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Hypospadias: A Comprehensive Review Including Its Embryology, Etiology and Surgical Techniques – Cureus

Hypospadias is a congenital deformity of the external genitalia in males. It is defined by the aberrant growth of the urethral fold and the ventral foreskin of the penis, which results in the incorrect location of the urethral opening [1]. In hypospadias, the external urethral meatus may be mispositioned to a different degree and may be accompanied by penile curving. Patients could have an extra genitourinary abnormality based on the location of the hypospadias [2,3]. It is considered among the most prevalent congenital abnormalities in males. Hypospadias occurs in one out of 150 to 300 live births [4,5]. After undescended testis, hypospadias is the second most common congenital abnormality [2]. Hypospadias is frequently characterized as posterior, penile, or anterior based on the preoperative location of the meatus. Nearly 70% of hypospadias are glandular or distally placed on the penis and are regarded as moderate variants, while the remaining are more severe and complicated. This classification was suggested by Duckett [6] (Figure 1).

The standards are used to define and evaluate hypospadias. Meatal position alone is widely regarded as a rudimentary method for classifying the severity of hypospadias since it does not consider the degree of tissue abnormality. In addition, the size of the penis, the size of the glans and urethral plate, the amount of separation of the corpus spongiosum, the existence of curvature, as well as abnormalities, and the location of the scrotum, have a substantial impact on the success of surgical correction. Consequently, a definitive classification can only be made following surgery [7].

This review article focuses on describing the embryological defects that cause hypospadias and the clinical characteristics of the condition. Outline the classification of hypospadias, its management options, the timing of surgery, and its results.

When penile growth is halted, it produces the three-fold classic triad of hypospadias, which includes a hooded dorsal foreskin, an inverted penile curvature on the dorsal side of the foreskin, and a proximal urethral meatus.

In the earliest weeks of embryonic development, the abnormal or incomplete closure of the urethra is the primary pathophysiological event that leads to hypospadias. Development of the external genitalia happens in two stages, which for both sexes are identical. In the first phase, which occurs between the fifth and eighth weeks of pregnancy, the primordial genitalia is formed in the absence of a hormonal stimulus. During this phase, mesodermal cells oriented laterally to the cloacal membrane produce the cloacal folds. These folds combine anteriorly to create the genital tubercle (GT), then break posteriorly into the urogenital and anal folds that surround the urogenital sinus. The GT is composed of three cell layers: the lateral plate mesoderm, the surface face ectoderm, and the endodermal urethral epithelium. This is the primary signaling center for GT's development, differentiation, and outgrowth [8].

In men with chromosomes XY, the second phase, a hormone-dependent stage, begins with the development of gonads into testes. Two of the most significant actions of testicular testosterone are the elongation of the GT and the formation of the urethral depression. The urethral plate, the distal section of the urethral groove, is delineated laterally by the urethral pleats and extends into the glans penis. The urethra is generated when the urethral folds merge, and the coat of the penis is created from the outer surface of ectodermal cells, which merge with the ventral part of the phallus to form the median raphe.

Various malformations, including hypospadias, an abnormal curve of the penis, and improper penile foreskin generation, can be caused by genetic disruption or change of signaling pathways in male external genital and urethral development.

Approximately 18.6 out of every 10,000 live births in Europe are affected by hypospadias. Registrations in 23 European registries between 2001 and 2010 demonstrated a steady number despite previously observed increases and decreases in temporal patterns [9]. North America has the highest prevalence, with 34.2 cases per 10,000 live births, whereas Asia has the lowest, at 0.6-69 cases per 10,000 live births. Even with more than 90 million screened newborns, the real global prevalence and trends are still difficult to quantify due to various methodological issues [5].

Given its frequency, hypospadias can place a significant strain on healthcare spending. A significant risk of complications may necessitate many procedures, particularly in the most severe instances. In addition, a substantial proportion of patients struggle with aesthetic or functional issues [2,10].

Concerning the genesis of hypospadias, several explanations have been offered, including genetic susceptibility, insufficient prenatal hormone stimulation, maternal-placental variables, and environmental impacts. Thus, it is plausible that hypospadias has several causes [11]. Premature birth, small-for-gestational-age newborns who are less than the 10th percentile for weight, length, and/or head circumference, and intrauterine growth restriction are risk factors. All of these have been linked to an increased chance of having a baby with hypospadias [12,13] (Table 1). Hypospadias rates have been linked to both inadequate placentas and the use of assisted reproductive technologies [14,15].

One in every seven occurrences of hypospadias is passed down through first, second, or third-degree family members. For anterior and middle forms, familial occurrence appears to be more prevalent than for posterior kinds. It is estimated that between 9 and 17% of the male siblings of a hypospadias-infected kid may get the condition [11]. One-third of hypospadias are directly linked to a genetic abnormality [16]. Nearly 200 disorders with recognized genetic etiology are connected with hypospadias. However, only a percentage of males with idiopathic variants have this condition [17]. The most common associations are WAGR syndrome, Denys-Drash syndrome, and Smith-Lemli-Opitz syndrome [2,18].

Another important factor in hypospadias is hormonal influence. Most hypospadias is solitary conditions, while uni-bilateral cryptorchidism and micropenis are related abnormalities [19]. These co-morbidities indicate a lack of hormonal effects during development. Androgens and estrogens both play a crucial role in genital development, and in the event of an imbalance, a range of congenital penile malformations, including hypospadias, micropenis, and ambiguous genitalia, can be observed [19]. A shortened anogenital distance in males with hypospadias as a consequence of a disturbance in embryonic androgen exposure [20] is a clinical observation that supports this notion. Other studies highlight the possible impact of so-called endocrine-disrupting environmental pollutants on the formation of hypospadias. Hypospadias was created in mouse models by the exposure of their mothers to synthetic estrogens. Due to the enormous variances across animals, it remains disputed whether someone has a significant effect on humans [21].

Hypospadias is among the most prevalent birth defects in males. A misplaced, ventrally-located urethral meatus; a ventral penile curvature; and an imperfect, dorsally-hooded foreskin are the physical exam criteria for diagnosing an ectopic urethral meatus. Hypospadias is a vast concept, however, and the degree of each symptom can vary significantly across boys. The second and third components are not usually present. Up to 5% of boys suffering from hypospadias have an undamaged prepuce, and the condition is not recognized till the foreskin becomes retractable or diminished during circumcision. Since an intact prepuce can conceal the existence of inadequate urethral growth in a newborn infant, it is essential to retract the foreskin before circumcision to prevent losing this oddity and presumably harming the imperfect urethra or expelling foreskin that could be incorporated into a subsequent urethral reconstruction [22].

Initial assessment of males with hypospadias must include a thorough medical history and physical examination. In conjunction with the trio of hypospadias, males may have related abnormalities such as penile torsion, penoscrotal webbing, and penoscrotal displacement, which must be taken into account while planning the surgery. On physical examination, boys with hypospadias may have dysplastic ventral tissue. On examination, a shortage of ventral axis skin may be instantly apparent.

The position of the urethral meatus has traditionally been used to determine the degree of hypospadias [7]. Using these criteria, almost 85% of males have a mild distal meatus variation [23]. Proximal hypospadias occurs in almost 15% of individuals and provides the surgeon with various distinct therapeutic issues [9].

A classification of hypospadias based only on the position of the urethral meatus is very simplistic and may even be deceptive. A classification system that incorporates the position of the urethral opening and the degree of penile curvature following degloving results in a more accurate and pertinent diagnosis.

The GMS score (glans meatus and penile shaft [curvature]) integrates physical exam outcomes in the operating room, evaluating the quality of the glans and urethral plate, the position of the urethral opening, and the degree of penile curvature, to objectively allocate scores for severity stratification (Table 2). The GMS score was designed for use in the operating room since office measures are less reliable in determining severity, namely the extent of ventral penile curvature [24,25].

Inguinal hernia, hydrocele, and cryptorchidism are the malformations most frequently linked with hypospadias. Inguinal hernia and/or hydrocele are up to 16% more prevalent [26]. Approximately 7% of individuals with hypospadias have cryptorchidism. With more proximal hypospadias, this jumps to approximately 10% [27]. Further diagnostic testing is recommended, such as an ultrasound of the urinary system and inner genital organs, to identify other nephro-urological anomalies [28]. Up to 14% of all hypospadias and up to half of the perineal hypospadias have a Mllerian remnant, resulting in catheterization difficulties, urinary blockage, or urinary tract infections (UTIs) following repair [29]. The majority of them are seen by ultrasonography. The American Urology Association cryptorchidism guideline suggests that all boys with unilateral or bilateral undescended testes and severe proximal hypospadias receive further testing to rule out a disorder of sexual differentiation (DSD), which is significantly more common in these situations.

The primary objective of hypospadias treatment is to restore both aesthetic and functional normalcy. Indications for correcting hypospadias comprise spraying of urine stream, inability to pee in a standing posture, curvature causing difficulties during intercourse, reproductive concerns due to trouble sperm deposition, and decreased pleasure with genital appearance [30].

The objectives of surgical repair in males with hypospadias comprise restoration of penile curvature to guarantee long, straight arousal, the extension of the urethra to enable proper flow of urine and sperm through the glans; and the development of an aesthetically normal penis. The surgeon must evaluate the defect's possible long-term importance and have an informed debate with the boy's parents about whether surgical intervention should be undertaken. In circumstances when the penis is straight when upright and the urethral opening is sufficiently distant to permit urination while standing, a repair may be of minimal value. To guarantee a satisfactory long-term outcome, continuing into maturity, repair should be performed with the fewest possible operations. This objective is attained by preparing the patient and family for the appropriate surgery, doing an accurate anatomic evaluation, and engaging in an open dialogue regarding the functional outcome and potential consequences.

Surgical timing is crucial. The timeframe of the repair should take into account the potential unfavorable psychological consequences of surgery, the anesthetic risk to the kid, the degree of penile growth that will assist a satisfactory repair, and the age-related changes in wound healing in boys [31]. The onset of genital awareness occurs at 18 months of life and increases with age [32]. Boys who had repair sooner (typically before 12 months of age) expressed less anxiety and had better psychosexual outcomes than boys who underwent repair later [33]. Boys who get corrective surgery at a younger age may also experience fewer problems, a result that underscores the need for early intervention [33]. In comparison, adult hypospadias surgery may be associated with a greater risk of complications [34]. In 1996, based on this research, the American Academy of Pediatrics Section on Urology advised that surgical intervention for hypospadias repairs be performed between both the ages of six and 12 months, with some exceptions in our current practice [35]. Given the seriousness and the necessity for numerous treatments, some standards place the best age for hypospadias correction within six and 18 months [30]. Those who did not recollect the operation were more likely to have a better body image and be content with their overall physical appearance. These findings relate to early-life surgery to reduce psychological load.

Aesthetic hazards, age-dependent tissue diameters, and emotional repercussions of genital surgery are all factors that have an impact [28]. When considering surgery for their young boy, many parents inquire about the appropriateness of anesthesia. In the last decade, disturbing discoveries about aesthetic-induced neurotoxicity in the growing central nervous system of rats have been reported. However, scientific concerns cast doubt on the applicability of these findings to people [36]. At two years of age, neurodevelopmental impairments were not detected in children subjected to anesthesia for hernia surgery, whether it was general anesthesia or regional anesthesia [37].

Therefore, the preoperative surgical evaluation with the boy's parents must include a thorough evaluation of the advantages of surgical repair against an age-appropriate explanation of the risks of general anesthesia.

Some anatomical characteristics, such as a short glans width and a thin urethral plate, are associated with greater postoperative problems and provide technical difficulty [38,39]. However, penile size is rarely considered a consideration in determining the ideal timing for hypospadias treatment, as penile development is minimal throughout the first few years of life. Therefore, delaying surgery appears to be without benefit [28].

In hypospadias surgery, the use of preoperative androgen stimulation is contentious. Some surgeons suggest testosterone supplementation for increasing anatomical proportions. Preoperative androgen stimulation in the form of dihydrotestosterone (DHT), human chorionic gonadotropin (hCG), or testosterone can be utilized to enhance the size of the glans and penis in preadolescent males [40,41]. It is believed that increasing glans size will reduce stress on the glansplasty and improve the amount of tissue accessible for urethroplasty, hence minimizing the risk of complications. Concerns associated with androgen stimulation in these boys involve abusive tendencies and behavior, enhanced erections, skin pigmentation, and secondary masculine characteristics. All traits are temporary and dissolve spontaneously, approximately six months following the final dosage [41]. Some surgeons omit preoperative testosterone as a consequence of the perceived greater risk of bleeding and enhanced angiogenesis. Others argue that the poor healing process may be attributable to subsequent androgen administration [42].

With more than 300 restorative surgical treatments documented in the present literature, it appears that a general strategy for hypospadias surgical correction is needed [43,44]. A reoperation rate of less than 5% is considered a good indicator of success. Hypospadias complications can occur in 5-10% of patients with mild variants and 15-56% of patients with severe forms, according to most estimates over the short term [3]. Short-term outcomes may not accurately represent the experiences of males throughout their adolescence. An accurate assessment of the long-term aesthetic and functional outcomes of the repaired penis cannot be made during a 12-month follow-up following surgery because psychosexual development and pubertal physical changes have not been completed [45,46].

Using magnification, atraumatic tissue manipulation, delicate equipment, suture materials, and proper hemostasis are the most fundamental prerequisites. In most cases, the anterior and middle hypospadias is corrected in a single procedure. On the other hand, a two-step treatment is frequently required for the posterior variant [3,28].

Intraoperative Assessment

Anesthesia does not signal the end of preoperative planning. Following antiseptic preparation and intravenous antibiotic treatment, the genitalia is scrutinized to decide the surgical strategy. Except for extremely severe cases of proximal hypospadias or subsequent surgical interventions, we do not perform cystoscopies on a normal basis. The preoperative evaluation of hypospadias should continue as described. The placement of the urethral meatus, the quality of the ventral shaft tissue, and the level of penile curvature are evaluated while the kid is sleeping. Depending on the extent of penile curvature, a circumferential incision is subsequently created, and the penis is partially or entirely degloved. Care must be taken to generate a mucosal collar by rotating inner glossy preputial tissue from the dorsolateral skin to the ventrum, where it is absent. This will help with ventral shaft skin covering and produce a more aesthetically pleasing outcome [47].

Penile Curvature: Diagnosis and Treatment

Whether or not hypospadias is present, a curved penile structure (chordee) may develop. The degree of curvature is a crucial factor in deciding between a one-stage and two-stage correction. The choice to treat men's scoliosis is based on their possible functional and aesthetic difficulties as they age into adulthood. Males suffering from untreated congenital curvature or Peyronie disease have been found to experience severe morbidity at even 20-30 degrees of ventral curvature, including difficulty with intercourse and patient displeasure with the look of the penis [48]. Curvature can be caused by reduced ventral skin, a small urethra, or the inherent curvature of the erectile body. Outside of surgery, it is exceedingly difficult to determine the source of curvature. The conclusive diagnosis is made with a simulated erection in the operating theatre after the penis has been degloved. Parents should be queried whether they see a history of penile curvature during erections and may even record this in their children with photographs. Before cutting the skin, the extent of curvature must be evaluated in the operating room. Through the insertion of a catheter into the meatus, the condition of the urethra and ventral skin may be determined. To remove dysplastic dartos tissue, a circumferential incision is created and the penis is degloved beyond the penoscrotal junction. Then, a mechanical erection should be conducted, often with a tourniquet inserted at the penoscrotal junction and a sterile normal saline injection [49]. Alternately, the surgeon can squeeze the corpora at the base of the penis to mimic an erection in tiny boys without the use of injections. In addition to saline injection, prostaglandin injection can be used to generate an erection [50]. Various approaches, such as unassisted visual examination and goniometry, which works as a protractor to reliably quantify the extent of penile curvature, are used to determine the degree of penile curvature. Other technological alternatives, such as tablets and applications, are beginning to appear.

Although there is no consensus about the treatment of particular degrees of curvature, the majority of surgeons appear to think that a dorsal plication is adequate for curvatures less than 30 degrees [51]. If the curvature is greater than 30 degrees, the urethra would need to be divided. A corporal curvature higher than 30 degrees at this point necessitates a corporal lengthening surgery that involves transection of the corpus spongiosum distal to the urethra or urethra transection [52]. As these males advance through puberty and experience more considerable penile development, their curvature may increase. Therefore, it is essential to diagnose and fix curvature during the first repair [53].

Distal Hypospadias Repair

Repair of distal hypospadias is one of the most frequent surgical operations performed by pediatric urologists, and several surgical approaches have been devised to treat this condition [47]. Different procedures are used to treat this condition.

There are a variety of repair operations that may be divided into advancement, tubularization, or the use of grafting and flap surgeries. Here, we are going to discuss the most commonly used surgical techniques in treating hypospadias.

The recommended surgical procedures for hypospadias correction may vary depending on the location of the meatus. Techniques such as the tabularized incised plate (TIP) urethroplasty, the Mathieu method, the meatal advancement and glanuloplasty incorporated (MAGPI), and the glans approximation procedure (GAP) are utilized to treat distal hypospadias.

It is possible to reconstruct the urethra in a single step or two. When feasible, the majority of surgeons now choose a single-stage operation. A single-stage technique is suitable for distal, mid-shaft, and proximal hypospadias without substantial chordee. When a single operation would not be adequate to correct a severe or perineal case of hypospadias with chordee, or when performing a difficult revision hypospadias surgery, a two-stage procedure may be necessary. The preponderance of surgeons now favors tubularization of the urethral plate as a one-step procedure [51].

The most prevalent single-stage technique is a Duplay-type operation with tubularization, with or without the vertical incision in the urethral plate, as described by Snodgrass [54].

The Thiersch-Duplay (TD) Repair

The Thiersch-Duplay (TD) repair, pioneered by Thiersch and later Duplay approximately 140 years ago, employs the brilliant notion of urethral tubularization of surrounding tissues distal to the misplaced meatus [55]. They completed their repair by producing a U-shaped incision from the penile shaft using vascularized skin and extending the meatus to the coronal edge. Later, for distant hypospadias, the restoration was covered with two layers of preputial skin [56]. This procedure comprises de-epithelialization of excess preputial skin and fastening across the repair to give a blood supply replacement. The next logical step was to stretch these U-incisions into the distal glans, tabularizing the glans itself over the repair, and providing a more aesthetically pleasing meatus at the penis tip [57]. The TD method requires a glans of sufficient width to accommodate a properly sized neourethral canal, at least one water-resistant layer, and glans flaps that may approximate over the repair. Parallel incisions are made 12 Fr in diameter lateral to the glans groove; the glans wings should be fully and extensively mobilized to enable tension-free covering. Under optical magnification, a dual running subcuticular suture is used to conduct neourethral reconstruction. If the child is circumcised, a de-epithelialized pedicle flap is harvested from the preputial tissue or the more proximal axis and placed over the complete neourethral restoration [58]. If the repair is more proximal, a double dartos flap can be obtained from the dorsal prepuce, with one flap running distally and the other flap running proximally. The circumcision defect is completed by approximating the glans wings into two layers (spongiosum and then epithelium), accompanied by the mucosal collar.

The Tabularized Incised Urethroplasty (TIP)

The TIP method, a variation of the TD, is a global standard surgical treatment for hypospadias. It was originally described in 1994 by Warren Snodgrass [59]. The surgical techniques are described below. A straight 8F sound is sent into the hypospadias meatus to evaluate skin covering across the urethra. In distal hypospadias, a demarcating incision is performed 2 mm proximal to the meatus, although a U-shaped incision may be prolonged proximally to healthy skin if necessary. Degloving the penis to the penoscrotal union. In every situation, an artificial erection is performed, as even coronal hypospadias is occasionally coupled with penile bending. If a minor chordee remains following skin release, dorsal plication is performed to rectify the corpora cavernosa's asymmetry. The tunica albuginea is incised longitudinally on either end just lateral to the neurovascular bundle opposing the point of curvature, followed by the placement of 6-0 Prolene sutures with the knots concealed. There is no need for substantial mobilization of the neurovascular bundle while performing dorsal plication. Next, 1:100,000 epinephrine is injected into the ventral glans at the visible intersection of the glans wings and urethral plate. Then, parallel incisions are made to detach the plate from the glans, and the glans wings are deployed laterally. Depending on its native groove, the plate is just 4 to 8 mm broad at this point. A linear relaxing incision is created from the inside of the meatus to the distal edge of the plate. This incision penetrates the epithelial surface of the plate and spreads deeper into the connective tissues underneath, reaching the corpus cavernosum. With the surgeon and helper maintaining counter-traction with tiny forceps, the plate is observed to be considerably widened upon division until further incisions offer no more mobility. Rather than a knife, tenotomy shears are indicated for this procedure so that an appropriate depth may be achieved without harming the corpus cavernosum. When the urethral plate is naturally grooved, the incision will be shallower than when the plate is naturally flat. Some surgeons perform the relaxing incision first, followed by parallel incisions to establish the plate's breadth. Despite this, this procedure regularly expands the plate to 13 to 16 mm, independent of its arrangement, assuring that the neourethra will be larger than 12F. If bleeding develops, epinephrine diluted 1:1000 is poured over the incision, and pressure is maintained for many minutes. If a tourniquet is required, it might be placed near the base of the penis. Electrocautery shouldn't be used to make holes in the plate or stop bleeding so that the plate's tissues and the corpora cavernosa underneath don't get hurt.

Next, a 6F stent is inserted into the bladder for urine diversion following surgery. The urethral plate is subsequently tabularized. To guarantee that the neo-meatus has a wide oval aperture, the initial stitch is always put at the level of the mid-glans, and no more than one or two stitches are removed distally. In this procedure, a single layer of 7-0 chromic catgut suture of full thickness is used. Those who prefer suture materials with a slower absorption rate might try subcuticular closures.

A thin dartos pedicle derived from the dorsal prepuce and shaft skin covers the whole neourethra. Glansplasty is then performed, commencing at the cornea and extending distally for a total of three stitches. Even though tiny sutures at the four and eight o'clock locations may evert the meatus somewhat for cosmetic purposes, securing the neourethra to the glans is not essential. The mucosal collar is approached in the midline, and the skin of the shaft is remodeled to resemble the median raphe. Subcuticular sutures are employed to avoid the suture tracts previously observed when 6-0 chromic catgut was put through the skin. After applying a dressing, the child is sent home [54].

Flap Methods

The Mathiew procedure is based on a meatal flap. This operation was documented for the first time in 1932, but it appears to have been performed earlier. The Mathieu method does not begin with penis degloving; rather, a penile shaft tissue flap is used to generate the neo-urethra. The Mathieu technique begins by determining the extent of the urethral gap from the meatus to the tip of the glans. Along the urethral plate, an equivalent distance is traced on the proximal penile shaft skin. An incision is created along these lines. For the proximal flap, an acceptable width of 7 to 8 mm is measured, with this width tapering to 5 to 6 mm towards the distal limit of the glans. After skin and glanular incisions, the shaft skin is degloved. The underlying tissue of the flap is dissected with care, enabling the flap to be advanced to the top of the glans. The flap is rolled over at the meatus and approximated to the lateral borders of the urethral plate with a running suture. Meatus has reached full maturity. The sutures are covered with a dartos flap of tissue, the glans wings are approached, and then a typical circumferential closure is done [60]. Concerns arise surrounding the vasculature of the utilized flap; if the flap's base is not adequately wide, the blood supply may be disrupted, hence increasing the prospect of fistula and stenosis. Others have expressed alarm at the fish-mouth look of the meatus. This method has been upgraded to the slit-like adjusted Mathieu (SLAM) process, which has shown favorable results, including an enhanced look of the meatus [61].

Advancement Techniques

Advancement methods do not necessitate tubularization of the urethral plate and are usually reserved for the most distal glanular meatus with minor penile curvature. Urethromeatoplasty employs the Heineke-Mikulicz concept, in which a longitudinal, vertical incision is made in the ectopic meatus and, subsequently, its margins are closed horizontally. This provides a cosmetically normal meatus and straightens the posterior urethral plate. This approach is especially beneficial in the presence of a stenotic, distal meatus with an accompanying blind-ending pit in the middle of a closed glans. The meatal advancement glanuloplasty would become one of the most often performed procedures to treat glanular hypospadias (MAGPI). The primary purpose of this operation is to distally advance the meatus without technically tabularizing the urethra [62]. The frequency of problems reported following the MAGPI technique complications occurs up to 10% [63]. Meatal stenosis and meatal regression are the most commonly encountered issues, while other uncommon complications consist of urethro-cutaneous fistulas and chordee.

The Glans Approximation Procedure (GAP)

The glans approximation method is a surgical approach developed for individuals with proximal glanular/coronal hypospadias who have a broad, steep glanular groove and a non-compliant or fish-mouth meatus, which is frequently found in the mega-meatus intact prepuce type [64].

Proximal Hypospadias Repair

The treatment of severe hypospadias has proven contentious. This disagreement persists as to the optimal treatment for proximal hypospadias. Numerous hypospadias correction procedures have been published, reflecting the difficulties of achieving optimal surgical outcomes for this illness [65]. Even though one-stage surgery has been shown to work for some types of proximal hypospadias, many people still prefer the more traditional two-stage method when moderate to severe chordee is present so that the length of the penis can be straightened during the first-stage repair.

One-stage proximal hypospadias correction often entails dorsal plication to restore ventral penile curvature and is one of many urethroplasty procedures. These can be differentiated according to the tissue employed in the repair, namely preputial skin, local skin, and buccal transplant. The preputial island flap is widely recognized as an innovation that Duckett contributed to [66]. In this procedure, the inner prepuce is elevated as a pedicle flap, translated ventrally, and used as an Onlay graft to cover the urethral plate following degloving the penis and straightening the chordee. Neo-urethras have a roof made up of the urethral plate. To prevent stricture development, the onlay excludes circular anastomosis. The inner prepuce is similarly employed as a pedicle flap in the Asopa variant of the technique, but the neo-urethra is left connected to the underside of the foreskin. Consequently, the skin and neo-urethra share a blood supply [67]. Higher complication rates were observed in the Duckett technique, and those included poor aesthetic results marked by excessive ventral bulkiness, penile torsion, and meatal anomalies; fistulas, strictures, total breakdown, and anterior urethral diverticuli formation [68].

The two-stage repair has been the preferred method of most surgeons for treating proximal hypospadias since the treatment of severe ventral penile curvature has shifted toward corporal lengthening techniques. Modern two-stage methods may be broadly classified, despite their many technical variants, into repair with free graft or repair with pedicle flap.

The Bracka two-stage repair is a urethroplasty technique that employs a free graft taken from the inner preputial skin or buccal mucosa [69]. STAG is an adaptation of Bracka's initial explanation [70]. In the first step, the penile curvature and urethral plate are rectified. A graft receiving bed is created by extending a midline incision into the glans. On the ventral penile shaft, compressive packing and patterning of the graft can reduce hematoma development and enhance graft uptake. Six months later, a U-shaped incision identical to the Thiersch-Duplay method is created, the urethra is tabularized, and glansplasty is carried out. Layered closure is performed to preserve vascular flow to promote healing [69]. The Byars flap treatment employs extra dorsal preputial skin, which is transferred ventrally with its vascular pedicle during the first surgery, as the urethral scaffold [71]. In the ventral part of the penis, the skin can be connected in the midline or positioned as a single unit, as in the STAG repair. In the second step, the neourethra is sealed by making a large U-shaped incision with a typical Thiersch-Duplay glansplasty. The development of a waterproof, two-layer closure and the establishment of a lumen of uniform diameter along the course of the urethroplasty are important technical elements. To guarantee that the neourethra retains a sufficient blood supply, several phases of closure are necessary. In particular, making a soft dartos bed above the clitoroplasty in the first step will ensure enough blood flow for the urethroplasty in the second step.

Regardless of the methodology, it is essential to evaluate the quality of the graft or flap during the second phase of the surgery. As an interim step, if skin deficit or tethering prevents safe closure, a dorsal inlay buccal mucosal transplant may be employed as an interim measure [72]. After graft harvesting, the urethra is rebuilt when all of the tissues are pliable. Alternately, the second step of repair can be performed simultaneously with a dorsal buccal graft inlay and a urethroplasty. It is essential to check that the penile curvature is rectified with a subsequent synthetic erection before urethroplasty. If needed, a dorsal plication or repeat corporal lengthening can be done to fix a slight curvature that keeps coming back.

The majority of early postoperative problems are caused by incorrect surgical techniques and may be readily avoided via improved procedure planning and tissue management.These problems include edema, hematoma development, wound dehiscence, flap decay, and fistula formation [73]. To prevent hematoma development, optimal hemostasis must be achieved. As previously stated, adequate tissue manipulation is required to prevent postoperative edema. A compression circumferential covering can also reduce postoperative edema.

There is a dearth of consistency in the literature when it comes to hypospadias correction procedures, as well as standardized definitions of problems and methods for evaluating outcomes [74]. Many questionnaires have been devised to evaluate the results of hypospadias treatment. Each questionnaire has its pros and limitations. These include the (Pediatric) Penile Perception Score (PPPS), the (Hypoplasia) Objective Scoring System, the (PedsQl), and the Hypoplasia Objective Penile Evaluation Score (HOPE) [75,76].

More than 70% of all patients who have hypospadias treatment are deemed cosmetically pleasing. More than 80% of males with repaired hypospadias had good sexual function [77]. However, these individuals are frequently prevented from initiating sexual interaction and frequently fear mockery due to the look of their genitals [77,78]. Symptoms of the lower urinary tract were twice as prevalent in individuals who had had hypospadias correction compared to controls [77]. After tabularized incised plate (TIP) urethroplasty, an obstructive urine flow pattern is usually observed, which may be due to aberrant elastic properties of the produced tube [79]. Almost 39% of patients who underwent proximal hypospadias surgery showed voiding problems, including hesitation and spraying [77]. Urinary problems (e.g., meatal stenosis, fistula, or urethral stenosis) may emerge years after the initial surgery; consequently, long-term follow-up is required [80].

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Hypospadias: A Comprehensive Review Including Its Embryology, Etiology and Surgical Techniques - Cureus

Embryology

Woman, 20, jailed in UK for taking abortion pills when abusive partner got her pregnant – The Mirror

The young mum says she was threatened with life imprisonment and a child destruction charge if she didn't plead guilty - and has described the horrors of her life inside

Image: Getty Images/iStockphoto)

A university student was jailed for two years after taking pills that caused her to have an abortion.

The young mum, who had a two year old daughter when she became pregnant again aged 20, told of her horror that she ended up behind bars.

She was charged with taking pills that caused her to have an illegal abortion.

I felt I had no other choice other than to (plead guilty), Laura, not her real name, told the Sunday Times.

The prosecution said if I didnt plead guilty, they would charge me with child destruction, and I would likely go to prison for life.

Image:

Last month the director of public prosecutions, Max Hill, was urged to urgently stop the prosecution of women who end their own pregnancies.

The number of women reported to the police for criminalised abortions has been on the rise with 30 so far in 2022 - already higher than previous years.

In an open letter signed by 66 organisations and people, including the British Pregnancy Advisory Service, barristers and womens rights groups, called for the prosecutions to stop saying women targeted are often "vulnerable" and in "desperate situations".

They pointed out that two women are facing prosecution in England now.

Referring to the US developments which saw abortion rights destroyed, the letter said: It is our strong belief that in the 21st century, in the shadow of the overturning of Roe v Wade, it is never in the public interest to prosecute women in these circumstances.

In reply Mr Hill said that abortion cases will be given an additional level of scrutiny from their lawyers before charges are brought against women.

While abortion is accessible, it is still officially a criminal act in the UK except in Northern Ireland, where it was decriminalised in 2019.

Under the Abortion Act and the Human Fertilisation and Embryology Act 1990, abortion is allowed up to 24 weeks of pregnancy if there is a risk to the physical or mental health of the women or her existing children.

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While there is no time limit for abortions if there is evidence of a fatal foetal abnormality or a significant risk to the mothers life.

But before an abortion can proceed, two doctors must ensure that the requirements of the Abortion Act are fulfilled, and they must both sign the certificate.

If a woman procures a miscarriage through medication without going through this process, it can be a criminal offence under the 1861 Offences Against The Person Act (OAPA). The maximum penalty is life.

New laws passed during the pandemic allow abortion pills to be taken at home up to ten weeks into a pregnancy but later abortions must be carried out in a medical setting.

But Laura is also calling for a change in the law, saying that women who have an illicit abortion only do so where someones in a very awful place in which theyve been given really no other choice.

The young mum eventually went on to graduate after serving a two-year prison sentence but says she still has nightmares about her ordeal.

Id never even had a detention at school. It was awful, she said.

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She said an abusive boyfriend told her not to go to the doctor but pills bought online instead.

At the time she believed she was eight to ten weeks pregnant when she climbed into the bathtub and gave birth.

I almost died, she says. I remember the bath being filled with at least an inch of blood.

I wanted to die. Honestly, I just felt like the whole world had just ended in front of my eyes.

She called an ambulance and was taken to hospital, where medics told her she had given birth to a 30-week foetus. According to the NHS, a full pregnancy is 40 weeks.

She admitted to the medics how shed taken abortion pills and police were called who guarded her bedside.

They actually had a police officer with me in the hospital the whole time and wouldnt let me speak to anyone other than the police, she said.

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She was only allowed a visit from her partner for 30 seconds when he whispered in my ear that he would kill me if I told anyone that he was involved.

They literally took me from the hospital, straight to the police station, she said.

Talking about her time behind bars, she said: I have seen things that no human being should ever see. The quality of life that those women have is disgusting. And I would not wish it on any single human being.

Ive seen people hang themselves. I have seen people slit their wrists and their legs, and people attack each other and over something so, so, so small.

Were in an environment with people who are vulnerable, and then mixed in with people who are violent. And that to me is not a safe place for someone like myself who is classed as vulnerable and very easily manipulated.

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Woman, 20, jailed in UK for taking abortion pills when abusive partner got her pregnant - The Mirror

Embryology

Woman gives birth to triplets with two-year age gaps between them – The Independent

A couple have finally welcomed the third baby in a set of IVF (in-vitro fertilisation) triplets, four years after the first sibling was born.

Karen and James Marks from Taunton, Somerset had had their first child a son named Cameron four years ago. Their daughter Isabella followed two years later.

Now, Karen has given birth to their final triplet, a daughter named Gabriella.

The children are considered triplets because they were all conceived on the same day, at the same time, and the same batch of embryos through IVF.

After Cameron was born in September 2018, the couple chose to keep the remaining embryos frozen so they could add to their family later.

Isabella was born in September 2020, and Gabriella on 3 July.

It feels so great to have all three of our children now, we feel so incredibly lucky, Karen said.

Some people go through IVF and sadly dont even get to have one baby, and weve managed to have three, so we just feel so lucky.

Gabi was our last embryo, so shes our last baby now. I knew I wasnt done before Gabi, so I told my husband if it didnt work, then we better get saving so we could have another one! I feel complete now, Im so happy. My heart is very full.

Around 390,000 babies have been born via IVF in the UK since records began in 1991, according to the Human Fertilisation and Embryology Authority.

Karen and James tried to conceive naturally for a year

( SWNS)

Karen said the couple turned to IVF after they tried to conceive naturally for a year but were unsuccessful.

Theres no specific reason. I dont ovulate regularly so thats the main thing, but other than that, theres no reason - we dont have any conditions, she explained.

The couple have shared their story to encourage others to try IVF if they are struggling to fall pregnant.

Infertility never leaves you, Karen said. Pregnancy announcements can still be painful, especially when someone has seemingly conceived easily.

Its a battle and a journey, and while part of me believes theres a reason we had to go through it, weve met so many wonderful people along the way.

If youve exhausted all other options, then crack on and go for it. Dont put it off or avoid it. Its the most likely fertility treatment to work, and it did for us.

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Woman gives birth to triplets with two-year age gaps between them - The Independent

Embryology

The earliest segmental sternum in a Permian synapsid and its implications for the evolution of mammalian locomotion and ventilation | Scientific…

Sternal morphology in Synapsida

The earliest-diverging synapsids, the paraphyletic pelycosaurs, do not preserve an ossified sternum in any known taxa23. However, a large, ossified interclavicle is always present. The broad interclavicle tends to be mostly uniform in shape (spoon-shaped asper Romer and Price23, with a cruciate anterior part and an elongate posterior rod). The first appearance of an ossified sternum in Synapsida occurs within the diverse and long-lived subclade Therapsida. Although some uncertainty exists as to the relationships between the major therapsid clades, the earliest-diverging group is generally considered to be Biarmosuchia24,25. Few biarmosuchian postcrania are known, but the sternum is preserved in a few taxa (e.g. Hipposaurus26), where it is unipartite and probably incompletely ossified. In known examples the sternum is relatively small compared to the interclavicle and roughly circular in outline (see Fig.1). No sternum is known in the Dinocephalia2,27. As several nearly complete dinocephalian skeletons are known e.g.28,29, it seems that the sternum, if present, must have been cartilaginous in this group, and the lack of discovered sterna is not simply due to incomplete preservation of the bony elements (likely also the case for pelycosaurs).

Anomodontia is the most diverse Permo-Triassic therapsid clade30, and also exhibits a diversity of sternal morphologies. Although an ossified sternum seems to be lacking in basal (non-dicynodont) anomodonts, as indicated by its absence in the well-preserved and fairly complete skeletons of Suminia31, Galechirus, and Galepus32, an ossified sternum is present in Dicynodontia30. In dicynodonts, it is always unipartite and generally a simple, plate-like element (e.g. in Diictodon20 and Eosimops33). However, the sternum is more complex in the burrowing dicynodont Cistecephalus (wide anteriorly, with a strongly tapering posterior edge and pronounced attachment sites for the ribs)19. In the largest known dicynodonts, the Late Triassic stahleckeriids, the sternum is extremely deep dorsoventrally, with a well-developed ventral keel6. The number of ribs attaching to the sternum varies in the clade, with one (e.g. Dinodontosaurus34), two (e.g. Aulacephalodon35), or three (e.g. Cistecephalus19) attachment sites per side.

Few well-described postcrania are known for Gorgonopsia. Previously-described gorgonopsian sterna consist of one element with up to three articulations for ribs on either side (i.e. in the holotypes of Lycaenops ornatus36, Aelurognathus tigriceps36, Aelurognathus microdon37, and Viatkogorgon ivakhnenkoi38). The discovery of an ossified and segmental abaxial sternal structure in Gorgonops torvus, however, raises the possibility that the apparently unipartite sterna of other species reflect incompleteness rather than the true absence of discrete sternebrae. With the exception of V. ivakhnenkoi, the aforementioned specimens were all collected and prepared in the early twentieth century, with damage to the more delicate parts of the anatomy. Also, although complete, well-preserved, and well-prepared, the skeleton of V. ivakhnenkoi is preserved on its side, and the base of the pectoral complex is poorly exposed, making the morphology of the sternum somewhat uncertain.

Similar to the condition in Gorgonopsia, few skeletons of Therocephalia are complete enough to determine whether a sternum was present. An ossified sternum appears to be absent in basal (non-eutherocephalian) therocephalians, as no trace of this element is present even in well-preserved, articulated skeletons of this grade (i.e. Glanosuchus39, Lycosuchus40). However, an ossified sternum is known in a number of eutherocephalian taxa (e.g. Regisaurus22 and Olivierosuchus21) and likely was present throughout that subclade41. In these taxa, the preserved portion of the sternum consists of a single element and is a remarkably large, plate-like structure dwarfing the interclavicle (Fig.1).

Prior to the discovery of the gorgonopsian specimen described here, the earliest record of an ossified multipartite sternum was in the Middle Triassic cynodont Diademodon tetragonus14. No ossified sternal elements are known in any earlier cynodonts (including taxa known from numerous complete skeletons, such as Thrinaxodon), suggesting that the sternum was cartilaginous in those taxa. Therefore, no conclusions can be drawn about the sternal shape in the earliest cynodonts. However, a multipartite sternum is known in several later-occurring non-mammalian cynodonts (e.g. the Jurassic Kayentatherium wellesi17 and Bienotheroides wansienensis18), in which the anteriormost section of the sternum is paired. Although rare, all the non-mammalian cynodont sterna thus far described consist of multiple elements. The connection between all these elements is assumed to have been cartilaginous18.

A fully-ossified multipartite sternum is known in several extinct mammaliaform taxa (e.g. Sinoconodon42, Maiopatagium43, Microdocodon9) (Fig.1) as well as all modern mammals44. Adult monotremes and non-crown group therians retain a distinct interclavicle, which acts as an anchor for the proximal attachment of the clavicle, and the first rib attaches to the largest anterior sternal element (the manubrium). Marsupials and placentals do not preserve an interclavicle as adults, as this element fuses with the manubrium during development. In these taxa, the clavicles and the first ribs both connect to the anteriormost sternal element on either side45.

The new multipartite sternum of a gorgonopsian presented here appears substantially earlier in geological time and is phylogenetically more stemward than any previous records of a mammalian-type sternum. The partial interclavicle shows some similarities to the interclavicles in other gorgonopsian specimens (see Supplementary Fig. S1) as well as those of Therocephalia (e.g. Olivierosuchus21), but the sternum of Gorgonops torvus is novel in its configuration.

The sternal variation within Synapsida discussed above allows us to distinguish between three morphologically differentiated groups:

Synapsids inferred to have an unossified sternum, such as pelycosaurs, dinocephalians, and basal anomodonts, therocephalians, and cynodonts. The lack of an ossified sternum in the predominantly large-bodied Dinocephalia demonstrates that sternal ossification is not necessarily correlated with body size.

Synapsids with usually large, unipartite (singular), and well-ossified sterna, for instance dicynodonts and eutherocephalians. Although it is possible that additional cartilaginous elements were present in life, the lack of a well-developed articular facet on the posterior margin of the sternum in these groups suggests that is unlikely.

Synapsids with segmental and ossified sterna such as Gorgonops torvus, Diademodon tetragonus, Mesozoic mammaliaforms, and extant mammals. The condition in close relatives of Gorgonops and Diademodon is uncertain, due to limited fossil data.

The discovery of the sternal complex of Gorgonops torvus now presents two equally possible hypotheses for the earliest evolution of the mammalian sternum: 1) the mammal-like condition arose first in gorgonopsians (as represented by Gorgonops torvus) but then was lost in eutheriodonts (therocephalians and cynodonts, in which the sternum ancestrally seems to have been cartilaginous) or 2) the condition in Gorgonops torvus evolved convergently to that of cynodonts, originating from a unipartite ancestral state common to both gorgonopsians and eutheriodonts. Until further discoveries of fossil taxa with different sternal conditions provide more evidence, it is impossible to test either of these hypotheses thoroughly, but functional considerations may provide some insight as to which is more likely (see below).

The sternum of extant mammals has several functions. Notably, it helps to reinforce the rib cage, with a more stable, enclosed rib cage offering better protection of the thoracic organs than one exposed abaxially46. Furthermore, an ossified (and hence stronger) sternum is functionally important for forelimb locomotor function, as the ventral surface of the thorax has major attachment sites for pectoral muscles47. These complementary functions of the sternum reflect its integral part in the entire system of the forelimb, the shoulder girdle, and the thorax. In synapsid evolution, there are two major morphologies of ossified sterna (Fig.1): the single, plate-like sternum present in earlier-diverging synapsids (e.g. dicynodonts) and the relatively narrow, segmental sternum seen in cynodonts such as Diademodon, some tritylodontids and mammaliaforms. The shift between these osteological configurations would have been part of a broader suite of functional changes occurring in this section of the synapsid tree.

The origin of mammals is associated with major changes in skeletal morphology, and the stepwise assembly of these changes in Permo-Triassic synapsids has historically been cited as one of the best bodies of evidence for macroevolution in the fossil record48,49. The inferred functional associations (and evolutionary drivers) of these changes can be roughly broken down into three areas: 1. dental (increasing complexity, both from differentiation in the heterodont tooth series, and from elaboration of individual teeth, particularly the postcanines, with multicusped and expanded crowns capable of occlusion); 2. cranial (formation of a complete secondary palate, loss of the postorbital bar, simplification of the jaw elements, increase in brain size/complexity); and 3. postcranial (increased regionalization of the axial column, changes in limb morphology associated with posture, origin of the segmental sternum). Each of these changes has functional implicationsmore efficient food processing driven by changes to the inferred muscular complement and jaw orientation for the craniodental characters50, and more active locomotion associated with an erect gait for the postcranial characters51. Each of these had downstream effects on portions of the anatomy not immediately subject to selection. For example, the expansion of jaw musculature attachment on the dentary is thought to have contributed to the decrease in size of the post-dentary bones and their eventual detachment to form middle ear bones52.

We offer a similar interpretation for the evolution of a segmental sternum in Permo-Triassic therapsids. On its own, this feature would have had little to do with improved gait in mammalsthe forelimbs themselves, the shoulder girdle, and the thoracic vertebral column all have more immediate influences on locomotion. However, the sternum bridges the girdle to the axial skeleton and it is thereforeconnected with shifts in locomotor evolution. And it is involved in two ways of particular note in the evolution of mammal-like morphologies and function: 1. increased regionalization of the axial skeleton and 2. increased posteriorization of thoracic elements. For the former, mammals are well known to have greater differentiation of the axial column into discrete regions than reptiles, although this transition is now thought to be more complex and to have occurred earlier in synapsid evolution than previously believed53. In the typical mammalian condition, the thorax is a highly discrete unit readily distinguished by vertebral morphology, and it also differs in range of motion from the cervical, lumbar, and caudal regions. By contrast, in many reptiles and even early synapsids, the distinction between the thoracic and lumbar regions is less evident, and the cervical-thoracic transition is also difficult to discern54. The origins of the mammal-like rib cage, a structure surrounding the thoracic organs (the heart, lungs and muscular diaphragm), are intimately associated with changes in gait that took synapsids from the lateral undulation of early amniotes to the primarily dorsoventral flexion of mammals47, in a divergent evolutionary path from the evolution of modern reptiles55. In the context of this paradigm shift in synapsid history, a massive, plate-like sternum broadly overlapping the interclavicle would have been a hindrance, a relic of the pelycosaurian condition with sprawling forelimbs in close association with the substrate. In the evolution of theriodonts (the group containing gorgonopsians, therocephalians, and cynodonts), even as early as gorgonopsians there is a shift towards more cursorial locomotion and more erect gaits, with a focus on dorsoventral rather than side-to-side motion51,55. To facilitate this style of locomotion, it was necessary to reduce the size of the pectoral girdle, thereby enhancing its mobility relative to the axial skeleton.

There are multiple ways to reduce the weight of bony elements, one being simply to not ossify them. This may have been the ancestral condition in eutheriodonts, given that the sternum seems to have been cartilaginous in the earliest therocephalians and cynodonts (although this would imply a reversal to the pre-theriodont condition in eutherocephalians). Another is to transform from a single solid plate to a series of connected elements, which can retain the protective function of the sternum without limiting mobility (similar transitions can be seen in the evolution of armor, with trends towards multipartite structures offering greater flexibility56). This latter approach appears to characterize sternal evolution in Gorgonopsia.

Greater flexibility of the thorax also has importance beyond permitting dorsoventral flexion during locomotion, as shown by Jones et al.53,55 in their studies of the axial skeletal evolution in Synapsida. Increased potential for axial twisting can also aid in behaviors such as grooming and fast locomotory maneuvers, but this requires vertebral specializations for torsion. In earlier non-mammalian synapsids (i.e. most non-cynodont taxa), the functional regions of the vertebral column are not as distinct as in later taxa such as advanced cynodonts (e.g. the Jurassic Kayentatherium55), and there is little evidence of selection for performance under torsion in the anterior vertebrae. However, a general phylogenetic trend towards more regionalization into pre- and post-diaphragmic areas of the vertebrate column can be observed even in more stemward portions of synapsid phylogeny55. A more flexible, segmental sternum, as seen in Gorgonops torvus, may represent a prerequisite for accommodating intervertebral torsion in the thorax.

Therefore, we hypothesize that the evolution of the ossified segmental sternum in Theriodontia is a part of the broad evolutionary shift towards more mammal-like locomotion, which may have facilitated the rise of this group as the dominant carnivores of the late Permian. Selection for a lighter, more flexible sternum in the context of changing posture, gait, and vertebral mobility can be inferred regardless of the homology of the segmental sternum in Gorgonopseither this morphology evolved convergently in gorgonopsians and eucynodonts, or it would represent an ancestral adoption retained in cynodont evolution (albeit cartilaginous in taxa other than eucynodonts).

However, posture and gait were not the only major changes in thoracic anatomy occurring in Permo-Triassic therapsids. The transition to a mammal-like thoracic morphology is also tied to the way for therapsids to break Carriers constraint: the respiratory limitation driven by dual use of the axial musculature during lateral flexion and costal breathing during rapid locomotion47. Dorsoventral flexion in mammals, and a more rigid thorax centered more anteriorly along the vertebral column, fundamentally altered synapsid ventilation, permitting both lungs to be expanded or compressed simultaneously, a metabolically more efficient method advantageous for active locomotion. For this to work, however, it is necessary that the dorsal and ventral limits (i.e. the vertebral column and sternum) of the bony enclosures of the lungs (i.e. the rib cage) are both strong and pliable, conferring functional advantage over a single stiff interclavicle-sternal plate in managing volume of the thoracic cavity57. A multipartite sternum with cartilaginous tissue between the manubrium and the sternebrae is consistent with this requirement. However, while this on its own would have helped to reduce the impact of Carriers constraint, actually breaking the constraint required an additional innovation: the diaphragm, a muscular sheet at the base of the thoracic cavity capable of pumping air through the lungs independently of locomotion.

Amongst the basic requirements for a diaphragm is that it must functionally be positioned caudad to the sternum, because by contracting during respiration, it creates negative pressure in the chest that is stabilized by the robust yet flexible complex of ribs, costal cartilages, and the segmental sternum. The origins of the diaphragm are obscure, however; it has been proposed to be unique to mammals or to have originated in some of the earliest pelycosaurs (e.g. caseids)58. Recent research taking data from developmental studies suggests that the diaphragm originated from ancestral pharygneal muscles of the cervico-thoracic region by posteriorization of elements associated with it, i.e. the forelimb bud during development and the brachial plexus nerve59. Accordingly, if the diaphragm did indeed originate from cervico-thoracic pharyngeal muscles, then the two requisite changes associated with the diaphragm may have been well underway in gorgonopsians: a) the posteriorization, evidenced by the likely presence of seven cervical vertebrae60 and the herein described elongate segmental sternum. And b) the elongate configuration itself of the sternum of Gorgonops, providing the needed caudad-positioned attachment for the diaphragm. This indicates that a mammalian-style diaphragm should already have been present in this taxon (and possibly, by inference, in theriodonts generally) to support the changes in ventilatory function.

Ontogenetic development of the sternum is well studied in extant mammals, with a particularly robust literature in the realms of human medicine and mouse embryology, demonstrating that formation of the characteristic segmental sternum is mediated by interactions with the developing ribs15,61. Specifically, the rib tips inhibit skeletal maturation, resulting in ossification of the intermediary regions but maintenance of cartilaginous connections between them62. As such, we must consider whether the segmental sternum would even have been selected for at all, or merely is an inherent consequence of developmental formation of a thoracic rib cage between the axial skeleton and sternum. Here, the fossil record is instructive. The plate-like sternum of dicynodonts has a variable number of rib attachments (see above), but a number of taxa clearly show multiple ribs attached to the single sternal element19. Therefore, it is apparently not an inherent developmental feature of Synapsida that rib attachments inhibit sternal growth and cause segments of the sternebrae to form. Rather, we propose that this system evolved through co-opting developmental mechanisms during a period of selection towards lighter and more jointed thoracic structures. Unfortunately, the cartilaginous nature of these elements in many synapsid groups (notably early cynodonts) makes it difficult to establish a precise understanding of the shift between dicynodont- and therocephalian-like structures and those of mammals. However, discoveries like that of the new Gorgonops specimen provide strong support for an early origin of the functional suite of derived mammalian locomotion and ventilation in the Permian antecedents of the clade.

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Embryology

Egg donors in the UK: What it’s actually like donating your eggs – Cosmopolitan UK

Over the past few months something strange has happened to my social media feeds. Rather than the relentless flow of ads for Shein, the all-mighty algorithm has decided that what I really need to see is endless posts telling me that I can be compensated 750 for donating my eggs.

Most of the adverts feature a happy couple (sometimes straight, sometimes gay) cooing over a baby. The captions are along the lines of Do an amazing thing and help others to start their family by donating your eggs! You will receive 750. Another ad features a grid of photos of a diverse range of women asking: Could this be you? as if theyre trying to recruit me to their gang of giving girls.

Typically, I scarcely pay attention to whats being pushed at me as I scroll, but this sudden overload of ads calling upon me to become an egg donor did have an impact. I stopped and questioned whether, actually, this indeed could be me.

And it turns out, thousands of women have wondered the same and decided that yes, it was the right choice for them. The UKs fertility regulator The Human Fertilisation and Embryology Authority (HFEA), is still collecting data for the past two years but in 2019, 4,433 IVF cycles were completed using donor eggs, with the figure doubling since 2009. The demand for eggs is high and social media posts are a quick and cheap way to reach potential donors, particularly from under-represented communities.

In one respect, the ads are spot on. Donating your eggs is an amazing thing to do and evidently helps thousands of people start a family. But, as with all ads, I was sure that the reality of donating was a little more complicated than a beautiful baby for a deserving couple, plus a 750 cheque for me. I wondered about the medical practicalities of donation, the long-term consequences, and costs. Most of all I wondered: have any donors came to regret this huge and irreversible decision? Is the 750 - which is by no means a huge sum - anywhere near worth it, or was it never about the money in the first place?

Three years ago, Izzie, 29 who works in admin, was also stopped in her tracks when she heard a friend of a friend discuss her experience of donating. Shed had a really positive experience and were very similar so I thought, maybe I could do this?

After reading blogs written by donors online, she quickly discovered that, as a mixed-race woman, her eggs would be in particular demand, due to a shortage of non-white donors. It was rare to see anyone who looked like me in the promotional material and I liked the idea of being able to help a family have a baby that looks like them, she explains to me over the phone.

Izzie says she had such a positive experience at her clinic (the Bristol Centre for Reproductive Medicine) that she donated again two years later. She especially appreciated the clear communication on offer and having to undergo what she called a fertility MOT.

This MOT is thorough and time consuming. After completing an online application form to see if they meet the eligibility criteria, donors forgo rigorous health checks testing their blood, urine, and ovarian reserve and an examination of their family medical history.

Donors also have a counselling appointment discussing the emotional and legal implications of donating. A range of topics are discussed, from the donors feelings around motherhood to whats motivating them to donate. She was shown leaflets written for children who were conceived through donation about how they came into the world.

It was very 'Mummy and Daddy wanted to have a baby but needed a bit of help', Izzie explained, laughing a little.

Florence OgramGetty Images

But according to Izzie the core point of the session was to explain that since 2005, donors have signed away their right to anonymity - meaning that once a child conceived through donation turns eighteen, they will be given access to their biological mothers name and contact details.

In her hour and a half counselling session Izzie was asked to consider challenging hypothetical questions: How would she feel if the child reached out in eighteen years time? What would she say if they wanted to be treated as a part of her family? How might she feel about this if she were to have her own children?

The crux of it was checking that Id actually thought about the implications of doing this and making sure I understood what I was signing up for and the possibility of being contacted down the line, she says.

Izzie found it interesting that the counsellor told her that at this stage, many women opt out after considering the real-life consequences of donating. That only goes to show how important this stage it, she adds.

At this point, Izzie also had the opportunity to write a message of goodwill to any potential child and a short profile of herself.

At first, I was quite stuck, but I put myself in the shoes of a child who might be curious about where they came from and that really helped. I told them how a looked, but also that I was a massive nerd at school and loved sci-fi and anime. I also made it clear that Id be very happy for them to approach me once they turn eighteen.

"I put myself in the shoes of a child who might be curious about where they came from"

The next stage of the treatment varies between clinics. Some artificially suppress the donors hormonal cycle, usually through a daily injection over a two-week period. Once the natural cycle is suppressed into an artificial menopause, donors are injected with hormones to boost the number of eggs produced, which lasts around 10 days. Then, a few days before collection, the donor will be given an injection of hCG which matures their eggs.

Other clinics work more within the donors natural cycle, skipping the two weeks of suppression injections. Then, instead of the hCG injection to mature their eggs, they use whats called a buserelin spike. This reduces the chance of ovarian hyperstimulation, a serious and potentially fatal reaction to fertility drugs, with symptoms including stomach pains, vomiting, and fainting. This method takes less time and has fewer medical risks so if you are considering donating, it is worth investigating which treatments are available

Finally, while under sedation (so, no eating that day!), the eggs are removed. The procedure takes about thirty minutes and donors feel discomfort or some pain for a few days afterwards, meaning things like sex can be difficult for a few weeks. The eggs will either be frozen, or if theyre used fresh (which increases the chance of conception) they will be mixed with a sperm sample that day usually from the intended father.

While the HFEA flags ovarian hyperstimulation as a potential risk, there is little research into the long-term health effects of donation. Although direct evidence is scant, some women have reported developing cancer or becoming infertile after donation, believing the treatment to have played a role.

A year on from her second donation, Izzie is still pleased with her decision; she knows a girl and a boy have so far been born using her eggs and although she is thrilled to have helped a family, Izzie doesnt feel any real connection to the children.

If you get very easily attached, I can see that might regret donating, she shares. You have to be not exactly cold, but detached and realistic about what it actually entails.

But what about those who didn't have as positive an experience as Izzie, or who aren't able to as easily separate themselves from the physical process?

Donating is a time consuming, invasive, and potentially dangerous process with relatively little compensation since it is illegal to sell your body parts in the UK. Here, donors are compensated up to 750 for their 'time', but the eggs themselves are given out of 'charity'. Meanwhile, in the US women can receive $50,000 per cycle. Naturally, this changes some of the factors motivating women to donate.

Liz, an American aged 43, went through three donation cycles in the mid noughties when her mother was facing eviction. I first thought of it after seeing an ad in a college magazine. I didnt respond to the flowery imagery telling me that donating my eggs would make me an 'angel'. I was purely motivated by the money as I was desperate, she tells me during a candid conversation.

Twenty years later Liz has come to regret her decision, not least since she believes it contributed to her developing an under-active thyroid. But crucially, another key difference between the UK and the States is that, according to Liz, donors are pressured to donate anonymously. Lizs donations may have resulted in birth of anything between zero and nine children, but she has no idea how many.

Ive struggled with this aspect of donating as I didnt know my father when I was growing up and Ive potentially put a group of children through the same thing, she adds.

Its an experience that Alicia, a 22-year-old opticians employee knows well. Born to an older, single mother, Alicia knew that she was donated through a sperm donation. But with her mother passing away when Alicia was seven, she was never told that she was also conceived using an egg donor. Then, last year she took a 23andme test and was connected to her biological mothers sister. After such a difficult childhood, Alicia has complicated feelings around her parentage.

I think when a lot of people donate, they consider the parents perspective, but they forget that theres going to be another human at the end of this who is going to have their own thoughts and feelings about it, she explains, adding that she now has a close relationship with both of her biological parents and even went to visit her biological father in the US.

Its bittersweet. We have a wonderful relationship but its hard that we were kept apart for so long. My biological mother and I are so similar, from the clothes we wear to the foods we hate. DNA goes so deep, and donors need to understand that, Alicia adds, remarking that on the other hand, she finds she has little in common with her aunt and uncle who raised her after her mothers death.

All UK donors are now mandatorily registered and donate in the knowledge that they may be contact by the donor conceived child in eighteen years time. However, Clare Ettinghausen of the HFEA (The Human Fertilisation and Embryology Authority) emphasises that in the days of 23andme, anonymity is far from a given and donors may be contacted sooner than they think.

Its an amazing thing to do and a truly selfless act, she told me, But you must seriously consider the lifelong implications of being a donor. And, as with all medical procedures, there is a risk and donors must do their research.

"I felt like a chicken being harvested for its eggs"

Some donors, however, have found that that their experience was not what they thought they were signing up to, even in spite of pouring time into researching the process.

Niamh was a twenty-year old veterinary student when she decided to donate her eggs at a clinic in Nottingham in 2018. However, she was disappointed with how she was treated by the clinic. During one ultrasound scan, the technician was struggling to find one of her ovaries.

They were pushing on me incredibly hard to the point that I was almost in tears. They didnt stop when I asked either. I felt like a chicken being used for its eggs, she recalls.

Despite this, after undergoing the final procedure, Niamh was overwhelmed with the desire to donate again, but this time with another clinic. She had a better experience with a London-based one but still felt that the needs of the intended parents were always put before hers.

Everything was done according to their schedule. They cancelled on me at the last minute several times and asked me to travel at short notice, so I lost money on train tickets, she shares. I also didnt realise that any travel costs would be taken out of the 750 compensation, which meant I received very little despite giving up a lot of my time.

Despite donating twice, Niamh now wouldnt recommend the experience to other women. Care really varies between clinics, and I think its up to the intended parents to demand better care for the donors we are doing for them out of charity, after all.

She and Liz have joined the online community We Are Egg Donors to spread awareness of the medical, practical, and emotional complications of egg donation.

Doctor Alexandra Price of the Bristol Centre for Reproductive Medicine clinic was saddened when I referred to some of these incidents. We really take the time to investigate if donating the right decision for them, she told me. We put our donors on a pedestal since we know its such a gift theyre giving we even give them flowers afterwards to thank them.

The joy brought by starting a family can be compared to little else and to be the person to enable that is an incredible thing. With women starting families increasingly late in life, the demand for egg donors will surely only increase over time too. However, donating your eggs is a complex and irreversible procedure. And as one donor told me: Once a baby has been born, it cant be unborn.

Ironically, my research into donation has only fed the beast and increased the influx of fertility clinic adverts into my timeline. But now, rather than picturing what I might do with 750, I see a child who looks like me. Who maybe even behaves like me but who was a total stranger. I feel unnerved and, although I admire the selflessness of all donors, I knew with absolute certainty that it's not for me.

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Egg donors in the UK: What it's actually like donating your eggs - Cosmopolitan UK

Embryology

Elon Musks Babies Were Conceived Via IVF And Surrogacy – Is It The Future Of Reproduction? – Forbes

Vitro Fertilization. IVF and Human fetus with DNA strand. 3d illustration

Advances in science and technology, coupled with modern medicine, has impacted the way in which we look at life. Reproduction is not an exception. It is no secret that the most prolific innovator on the planet, Elon Musk, took an engineering approach to reproduction, and his first five boys came into this world via IVF, and the last girl was delivered using a surrogate mother. The Tesla mogul and his former wife, author Justine Wilson, welcomed son Nevada Alexander Musk in 2002. Nevada died of sudden infant death syndrome, or SIDS, at only 10 weeks. After losing their firstborn, Musk and Wilson turned to IVF to grow their family. She gave birth to twin sons Griffin and Xavier Musk in April 2004. The couple also used IVF to welcome triplet sons Kai, Saxon and Damian in January 2006. Later on, Musk began dating singer Grimes, who gave birth to their son X AE A-XII. Earlier in March, Grimes revealed that she and the SpaceX founder had welcomed their first daughter, Exa Dark Siderl Musk, via surrogate in December 2021. And there are claims that Elon and Amber Heard had a legal battle around the cryopreserved embryos. In recent weeks rumors surfaced that he had two more kids with the board member of OpenAI and executive at Neuralink. Sex of the babies was not disclosed. Considering how busy Elon is, business ethics of such a relationship, and the fact that there are two babies, there is a chance that he just served as a donor.

While this approach raises many ethical questions including: Were his first babies selected to be male at the preimplantation stage?. While there are regular attempts to build moral and ethical framework for allowing sexing for non-medical reasons, sex selection is illegal in many countries. We recently observed one of the IVF boys taking matters into his own hands changing both name and gender and distancing herself from her father. A very brave move deserving recognition and support.

Elon Musk is not the only one opting for IVF instead of the traditional approach. Several people in my network recently told me that they chose IVF and surrogacy. Some decided to do this to improve the chances of having a healthy baby. One of my friends decided to reproduce via a surrogate to have undisputed legal rights and ensure that his plans to invest substantial resources into the upbringing and education of their offspring do not go down in flames due to the unexpected divorce. And some chose surrogacy for health reasons.

Also, there is a myriad of startups working on reproductive health and longevity including the two I recently covered, Dr. Dina Radenkovics Gameto, and Oviva, and several research groups and startups are working on artificial wombs.

Can this method of reproduction become mainstream? Are we going to see this trend accelerate as the artificial uterus technology matures and the natural reproduction declines? Lets take a closer look at this emerging and rapidly expanding field.

LONDON, ENGLAND - FEBRUARY 2003: A sperm fertilizes an egg under a microscope using ICSI (Intra ... [+] Cytoplasmic Sperm Injection) as part of IVF treatment at the private Lister Hospital. One needle holds the egg in position while the other needle injects a single sperm into the egg to fertilize it. The technique is used for male infertility. (Photo by Tina Stallard/Getty Images)

Louise Brown in 1978 became the worlds first baby to be born by in vitro fertilization, or IVF. Her birth revolutionized the field of reproductive medicine. Given that approximately one in eight heterosexual couple has difficulty in conceiving, and that homosexual couples and single parents need clinical help to make a baby, the demand for IVF has been growing. In fact, IVF is so common that over 5 million babies have been born through this technology. On a side note, critics of cryopreservation should note that these babies were cryopreserved before they were implanted...

COVID has also changed the way we view reproduction and IVF. Pew Research estimated there were close to 300,000 fewer births in the U.S. in 2021 as a result of the pandemic and low levels of sexual activity. Many women of reproductive age were perhaps worried about the vaccine, or were concerned about the vaccines effect on future fertility, current pregnancy, and breastfeeding, among other concerns. During the pandemic, there was a decline in the number of concluded assisted reproductive technology cycles as compared to the previous years. This decline can be attributed to many factors: the local restrictions and the fear about SARS-Cov-2 infection, being among the primary. However, a study published the same year by the National Center for Biotechnology Information reported that couples are actually prioritizing IVF treatment in the post-COVID era. No information exists in the literature regarding the effect of coronavirus on the IVF cycle attempt. In fact, a study titled Does COVID-19 infection influence patients' performance during IVF-ET cycle?: an observational study concluded that COVID did not affect patients' performance or ovarian reserve in their immediate subsequent IVF cycle. There needs to be more data available on IVF, both pre and post COVID.

In order to understand IVF, we first need to look at the natural process of reproduction. Believe it or not, it all starts in the brain. Roughly 15 days before fertilization can happen, the anterior pituitary gland secretes follicle stimulating hormone (FSH), which ripens a hand full of follicles of the ovary that then release estrogen. Each follicle contains one egg, and on average only one follicle becomes fully mature. As it grows and releases estrogen, this hormone not only helps coordinate growth and preparation of the uterus, it also communicates to the brain how well the follicle is developing. When the estrogen level is high enough, the anterior pituitary releases a surge of luteinizing hormone (LH), which trigger ovulation and causes the follicle to rupture and release the egg. Once the egg leaves the ovary, it is directed into the fallopian tube by the fimbriae. If the egg is not fertilized by the sperm within 24 hours, the unfertilized egg will die and the entire system will reset itself, preparing to create a new egg and uterine lining the following month.

The egg is protected by a thick extra cellular shell of sugar and protein called the zona pellucida. The zona thwarts the entry and fusion of more than one sperm. Each ejaculation during sexual intercourse releases more than a 100 million sperm. But only a 100 or so will make it to the proximity of the egg, and only one will successfully penetrate through the armor of the zona pellucida. Upon successful fertilization, the zygote immediately begins developing into an embryo and takes about three days to reach the uterus. There it requires a couple of days to implant firmly into the endometrium, the inner lining of the uterus. Once implanted, the cells that are to become the placenta, secrete a hormone that signals to the ovulated follicle that there is a pregnancy in the uterus. This helps rescue that follicle, now called the corpus luteum, from degenerating, as it normally would do in that stage of the menstrual cycle. The corpus luteum is responsible for producing the progesterone required to maintain the pregnancy until six to seven weeks of gestation when the placenta develops and takes over until the baby is born approximately 40 weeks later.

In patients undergoing IVF, FSH is administered in levels that are higher than naturally occurring, to cause a controlled over-stimulation of the ovaries so that they ultimately produce multiple eggs. The eggs are then retrieved before ovulation would occur, while the woman is under anesthesia, through an aspirating needle guided by ultra-sound. Most sperm samples are produced by masturbation. In a laboratory, the identified eggs are stripped of surrounding cells, and prepared for fertilization in a petri dish.

Fertilization can occur by one of two techniques. In the first, the eggs are incubated by thousands of sperm and fertilization occurs naturally over a few hours. The second technique maximizes certainty of fertilization by using a needle to place a single sperm inside the egg. This is particularly useful when there is a problem with the quality of the sperm. After fertilization, embryos can be further screened for genetic suitability, delivered into the womans uterus via catheter, or frozen for later attempt at pregnancies. This last process is also called embryo cryopreservation. It involves freezing of the embryos. You may choose to freeze extra embryos and use them later if you: postpone or cancel implantation into your uterus after an egg is already fertilized; want to delay IVF to a later date; want an option in case early attempts at fertility treatment fail; or choose to donate unused embryos to other people trying to get pregnant or to researchers rather than destroy them; or for other reasons.

If the womans eggs are of poor quality due to age or toxic exposures or have been removed due to cancer, donor eggs may be used. In the case that the intended woman has a problematic uterus or lacks one, another woman, called the gestational carrier, or surrogate, can use her uterus to carry the pregnancy. To increase the odds of success, which are as high as 40% for women younger than 35, doctors sometimes transfer multiple embryos at once. Which is why IVF results in twins and triplets more often than natural pregnancies. However, many clinics seek to minimize the chances of multiple pregnancies, as they are riskier for mothers and babies.

Millions of babies like Louise Brown have been born from IVF and have had normal, healthy lives. The long-term health consequences of ovarian stimulation with IVF medicines are less clear. In fact, it is possible to avoid the many genetic abnormalities with preimplantation diagnosis. The Human Fertilisation and Embryology Authority of the U.K. published a blog in which they declared that IVF is generally safe, adding that most people who have it experience no problems with their health or pregnancy. They do mention some risks that people should be aware of, including: ovarian hyperstimulation syndrome, having a multiple pregnancy or birth, and having an ectopic pregnancy. The American Society for Reproductive Medicine also notes that although serious complications from IVF medicines and procedures are rare, there are still some risks from injectable fertility medications. Though so far, IVF seems safe for women. Because of better genetic testing, delayed child-bearing, increased accessibility, and diminishing costs, it is not inconceivable that artificial baby-making via IVF and related techniques could outpace natural reproduction in years to come.

Clearly, IVF is gaining popularity every year. According to a 2015 report by the U.S. Society of Assisted Reproductive Technology (published in 2017), one million babies born in the U.S. between 1987 and 2015 were born through the use of IVF or other assisted reproductive technologies. There are many agencies and centers worldwide that provide these services. Some examples of these agencies are: Circle Surrogacy & Egg Donation, Brilliant Beginnings, The Center For Surrogacy & Egg Donation, ConceiveAbilities, Hatch Egg Donation & Surrogacy, and Growing Families. Others include Ambroise Par Group, AMP Center St Roch, AVA Clinic Scanfert, Bangkok IVF center, Betamedics, Bloom Fertility and Healthcare, Bourn Hall Fertility Center, and Biofertility Center and Chelsea and Westminster Hospital.

Like IVF, surrogacy too is becoming a very popular way to have children, particularly for wealthy couples in the West. According to a 2019 WebMD blog post, about 750 babies are born each year using gestational surrogacy. Similarly, PBS reported that in 2018 over 100 children were born in Boise, Idaho, through surrogacy. In Canada, surrogate births have increased by 400% in the last decade. Even celebrities are doing it! News anchor Anderson Cooper used a surrogate for the birth of his son, as did Sir Elton John, who used a surrogate for the birth of his two sons. Other celebrities like Kim Kardashian, Robert De Niro, George Lucas, and Neil Patrick Harris used surrogates too.

Three generations of women and a robot jumping for joy

There are several reasons why IVF and surrogacy are fast becoming a new way of family planning. Infertility is one of the main reasons why prospective parents opt for surrogacy. Another reason why would-be parents opt for surrogacy is the age factor because age plays a big role in a persons ability to conceive and carry a baby. Likewise, same-sex couples and single individuals who are unable to conceive a child naturally may choose to turn to a surrogate. Some people may also have medical or physical problems that dissuade them from pregnancy or make birth impossible. At the end of the day, it is a personal and private decision.

Interestingly, many in the generation X and Y are reproducing via IVF after going through a divorce. Recently I spoke with one of my friends in the venture capital world who is looking at IVF via a surrogate as a way to avoid the possible legal problems in the case of a future divorce. "I am planning to go to buy a few egg cells from a very accomplished young scientist and use a service in Georgia (country) to get a surrogate. I want to have a very smart kid that I will invest a lot of resources, time and energy in and I won't need to share custody over the kid in the case I break up with my girlfriend," said an accomplished man in his mid-forties who refused to be named in the article. "I went through a very painful breakup once and how I have to share custody of a child and don't have full control over the upbringing. But children are our legacy and I want to ensure that I can raise the child to be a great person, give great education, and provide amazing care without being pulled into a difficult relationship with the mother. I am sure that my girlfriend will invest a lot of energy into this child or I will find another girlfriend."

This statement shocked and puzzled me.

Recently, I covered a startup called Gameto, run by Dr. Dina Radenkovic, a wonderful physician turned VC turned CEO. "The reproductive industry is up for disruption. We are going to help millions of women get the freedom to have babies without the time pressure. And postpone menopause. But I am also investing in a company developing artificial uterus technology. In the future, painful childbirth may be optional and without the need of a surrogate, she told me.

And females also get a lot of freedom to choose the genetic background of their children. Many are choosing to reproduce using the sperm from the validated, healthy, intelligent, and accomplished individuals.

Same week I met a wonderful scientist, a recent PhD from Harvard who also works in the field of reproductive health. "You know, I am an open ID sperm donor. It helped pay my bills during the school years and now I have over 35 confirmed kids worldwide, he said.

A sperm bank is a facility or enterprise that collects and stores human sperm from sperm donors for ... [+] use by women who need donor-provided sperm to achieve pregnancy. (Photo by Evan Hurd/Corbis via Getty Images)

There are few reliable figures on the sperm banking industry and the percentage of donations that are made anonymously. Researchers find it difficult to track how many men have donated sperm, and how many children have resulted from each individuals donation. Approximately, there are about two dozen sperm banks in the United States; each operates independently and with minimal government oversight. Some of the famous ones include Cryos International and California Cryobank. There are others also.

Some of these operations are pretty cryptic and shady. Many clinics have revised their policies not to eliminate anonymous donations, but to make clear that the term only means they will not share donor information. Others are moving toward open ID donor systems, in which donors are told that offspring could connect with them when they turn 18 or sooner if both parties agree to it.

As debates about womens bodies and their right to choose continue to rage throughout the world, surrogacy laws remain in infancy. The laws also change as reproductive technology and the very meaning of a parent changes. In the U.S., there isn't a federal law on surrogacy and state laws vary. Some states have written legislation, while others have common law regimes to deal with surrogacy issues. Surrogacy friendly states facilitate surrogacy and surrogacy contracts while others simply refuse to enforce them. Some states only facilitate married heterosexual couples. States that are considered to be surrogacy friendly include California, Illinois, Arkansas, Maryland, Oregon and New Hampshire.

Surrogacy has become so popular that it has given birth to a new form of tourism called reproductive tourism or cross-border reproductive care. This multibillion-dollar global industry is perfect for price-sensitive, middle-income would-be parents. The surrogates in this case are usually those who are thought to be of low socioeconomic status in countries like India and Nepal. In India, surrogacy may be worth about $400 million each year, driven by the countrys nearly 3,000 specialty clinics. Thailand, Ukraine and Russia are other popular sources of surrogates for international clientele. Thus, surrogacy is the route to escape poverty for many women in these developing states.

Research on the development of IVF and reproductive technology is still in infancy. However, as it becomes more advanced, we are likely to see more non-traditional families and the reality is probably closer than we think. And with the changing trends in family planning, there is no doubt that science and technology will continue to progress and change the way we live and think. Before we know it, this new trend and demand for babies is likely to further advance science and the procedures. Perhaps in the future, women will not need to go through the painful process of childbirth.

Go ahead and continuously improvement concept, silhouette man jump on a cliff from past to future ... [+] with cloud sky background.

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Elon Musks Babies Were Conceived Via IVF And Surrogacy - Is It The Future Of Reproduction? - Forbes

Embryology

Handful of Tories declare themselves as candidates to replace Johnson – Morning Star Online

THEresignation of Boris Johnson as prime minister has seenattention turntowho will replace him.

Only a handful of Tories have so far declared themselves candidates, although a number of others are thought to be set to do so.

Attorney GeneralSuella Braverman and Commons foreign affairs committee chairman Tom Tugendhat have confirmed their intention to stand while Steve Baker has said he is seriously considering standing.

Ms Bravermantook the unusual step this week of calling on Mr Johnson to resign, saying that she would not be stepping down but at the same time throwing her hat into the ring as his potential successor.

Mr Tugendhatlaunched his leadership bid with an article in the Daily Telegraph today, promising tax cuts and new energy and ideas for government.

"I have served before in the military and now in Parliament. Now I hope to answer the call once again as prime minister, said the former soldier, who has been a prominent critic of Mr Johnson and an advocate of a more aggressive foreign policy.

Former chancellorRishi Sunak also unveiled his candidacy today, the most high-profile figure so far to do so.

Foreign Secretary Liz Truss, former health secretarySajid Javid, ChancellorNadhim Zahawi, health and social care select committee chairmanJeremy Hunt and Transport SecretaryGrant Shapps are all expected to enter an increasingly crowded field.

More declarations are expected in the coming days, but some senior Tories have already said that they will not be standing, including former levelling up secretary Michael Gove, Deputy Prime Minister Dominic Raab and disgraced former health secretary Matt Hancock.

Another candidate yet to confirm, but already installed as the bookies favourites, is Defence Secretary Ben Wallace.

Polling of Tory Party members by YouGov also puts Mr Wallace in pole position, where he beats all of the main presumed contenders.

Mr Wallace, who served in the Scots Guards, has had a prominent role in Britains response to the Russian invasion of Ukraine.

However, he has one of the worst voting records on LGBT rights in Parliament.

He has opposed every piece of LGBT legislation put in front of him, including same-sex marriage and the Equality Act.

Mr Wallace also voted in favour of the Human Fertilisation and Embryology Bill, which, had it passed, would have made it harder for lesbian couples to conceive children through IVF.

Hehas also repeatedly opposed raising welfare benefits and has always backed more hard-line immigration and asylum laws.

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Handful of Tories declare themselves as candidates to replace Johnson - Morning Star Online

Embryology

Y Combinator-Backed Lilia Launches A More Convenient And Affordable Egg Freezing Offering Built For The Millennial Women – Forbes

While a womans age at thaw has relatively little impact on a womans chances of success, the age at ... [+] freeze does, according to the U.K.'s Human Fertilisation and Embryology Authority

Lilia, a full-service egg freezing concierge, today announced they are now offering egg freezing directly for their clients at nearly half the price of an average IVF procedure and in half the time, and coordinated to make the experience less isolating. With this new breakthrough offering, women have access to the leading, most progressive doctors in the country dedicated to Lilias mission of giving every woman the freedom to make her own decisions on her own timeline.

According to the Human Fertilisation and Embryology Authority, the U.K.'s independent fertility regulator, the data shows that while a womans age at thaw has relatively little impact on a womans chances of success, the age at freeze does, with evidence showing that if eggs are frozen below the age of 35, the chances of success will be higher than the natural conception rate as the woman gets older.

Alyssa Atkins, founder and CEO of Lilia

As a Y Combinator graduate, and having raised roughly $1.5 million to date, Lilia is revolutionizing how women plan their futures. Founded in 2019 by Alyssa Atkins, who froze her eggs at the age of 29, the idea for Lilia was conceived when she founder realized the whole experience was built for an IVF couple, not young women focused on their futures. The company is currently operating with doctors in New York City, Chicago, and San Francisco, with plans to go national by the end of 2023. As explained by Atkins, Lilia is now a single point of contact for women - no more waiting on hold for doctors offices or fielding a million emails from the clinics different departments.

The convenience of Lilias offerings is reflected in the fact that they coordinate everything for the patient from contracts, to appointments, meds, and virtual consulting and prep work. The whole process, Atkins highlights, takes less than a month. And lets be honest until now, no one has focused specifically on serving the millions of women aged 24 35 for whom egg freezing works best.

Most women have considered freezing their eggs at some point and many have been thinking about it for years. But when they turn to Google, they are bounced out by the complexity of how to start, where to go, or what to do. Egg freezing, when done early, is the best way to relieve reproductive pressure and give women more optionality. Optionality is freedom and freedom is everything for women who dont want to be pressured into having a child before they are ready.

Lilia is changing a stale narrative about what a womans life ought to look like. Society is pretty prescriptive about its expectations of women college, career, marriage, baby in that order and ideally by 30, which leaves most women feeling behind no matter what theyve accomplished or what their personal goals are, explains Atkins.

Its 2022 (in case you havent noticed) and its time we usher in a new normal. One where egg freezing isnt perceived as something you do in your late 30s as a last resort, but something you can do early, in your 20s, because you have the right to reproductive freedom, autonomy, and choice. Its not just something to be done for your future self; it has real and direct impacts on the present you by taking the pressure off, especially in dating. With eggs secured early, women dont have to rush; every first date isnt an evaluation of whether the person in front of you is the future father of your children.

Atkins admits she sees so many women in their late 30s saying they wish someone had told them to freeze their eggs earlier. So, she and her team are working on showing women how common and normal this process is and educating them along the way. People think egg freezing is about the future you, but really its about taking the pressure off of you today because it lets you date differently, make different career moves, and live with more freedom, she adds.

It is more important now than ever that women have the power of choice and freedom. Choice over whether they take certain jobs, and when or whether to have kids at all. They deserve the freedom not to settle, to stop doing the dating math, and not to be rushed in making important decisions about their careers or matters of the heart. Every woman deserves the feeling of freedom and inner peace that comes from knowing all doors to her future are open, continues Atkins.

So who are Lilia's users and target audience? Obviously, someone for whom being a biological mom is incredibly important, and they want to ensure this happens at some point in their lives. Perhaps its a woman who knows she wants to use a surrogate at some point and so egg freezing is a path to this; startup founders, who are super busy and want kids but know they need time to build their companies first; women who arent sure they want kids at all, but want the option later; basically, any woman who wants to take the pressure off and keep their options open.

We believe that in time, egg freezing will be as common as birth control, and it should not only be a luxury for a small group of society. While egg freezing might not have been part of our fairy tale stories growing up, it has become extremely common and is one of the most radical acts of self-care a woman can make. We don't want women to wait until egg freezing becomes an absolute emergency, at which point its either often too late to retrieve enough healthy eggs, or to do so would require many cycles and the corresponding costs that come with it, adds Atkins.

Lilia is under the medical leadership of Dr. Roohi Jeelani, who does the highest volume of ... [+] egg-freezing retrievals in the country

The time and cost savings are created to let the company deliver an outstanding experience to women for a predictable $9,000 all-in, instead of the nebulous $15,000+ women are usually faced with. Under the medical leadership of Dr. Roohi Jeelani, who does the highest volume of egg-freezing retrievals in the country, Lilia is able to deliver this breakthrough offering while maintaining the highest standards in medicine.

We have carefully selected clinic partners who are equally committed to making egg freezing affordable and accessible to all, and dedicated to together creating a better experience for women.

Atkins and her team spent a lot of time getting the offering right, ensuring they could drive down costs and improve the experience while maintaining a superlative standard of care. Now that theyve done this, theyre working on changing the entire narrative around egg freezing and normalizing this process as a regular part of womanhood.

Were especially interested in how dating and egg freezing relate, because we know when women freeze eggs early theyre able to date differently and that it gives them more power in their love lives. Were working on telling more womens stories about whove frozen their eggs so women see just how common this is. Something I realized when I froze my eggs is I had all these friends whod done it but werent talking about it, concludes Atkins.

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Y Combinator-Backed Lilia Launches A More Convenient And Affordable Egg Freezing Offering Built For The Millennial Women - Forbes

Embryology

The End of the Beginning of the End of Abortion | Hadley Arkes – First Things

The decision today in the Dobbs case, long awaited from the Court, can be appreciatedand savoredas a resounding first step. To rephrase Churchills line, we might say that we are only at the end of the beginning in dealing with the turbulence that abortion has imparted to our political life for the past fifty years. That turbulence promises to rise now to new levels of enmity, until our people can regain some moral clarity on the taking of innocent life in the womb. But something good has been done, and there is an analogy here to the Emancipation Proclamation:It freed only the slaves held in states at war with the national government;it did not free slaves held in border states such as Delaware.And yet it became clear that it was animated by an anti-slavery impulse, and thats how it came to be understood.In the same way, this decision will be seen as a decision affirming life. It will be seen as inviting legislatures in the states to begin casting the protections of the law over the unborn child in the womband it will do that even though the conservative majority goes out of its way to avoid any such invitation or encouragement.

Still, the decision will be seen as a pro-life proclamation even as abortions proceed at a massive level in the blue states.Our disappointment here mirrors that of people on the other side:They are feeling dispossessed, because they thought they bore nothing less than a constitutional right, which does not go in and out of effect when they move from one state to another. And for our part, we lament the fact that the Court does not move to put the critical anchoring point in place as it sends the matter back to the states: Namely, that as we draw on the objective facts of embryology, that offspring in the womb has never been anything less than human from its first moments, and not merely a part of the mother. If that predicate were put in place, there would be a clearer understanding of what makes it deeply justified for the laws in the states to cast their protections over the child in the womb. And what makes it warranted in turn for Congress and the federal courts to act when the protections of the law are withdrawn from a whole class of human beings in the states.

But the majority in Dobbs conspicuously held back from putting that premise into place. And that is why the dissenting opinion by Justice Stephen Breyer makes no contact with the opinion he is ostensibly opposing. Breyer charges that the Court today says that from the very moment of fertilization, a woman has no rights to speak of. A State can force her to bring a pregnancy to term, even at the steepest personal and familial costs. And yet that is what Justice Samuel Alito and his colleagues sought carefully to avoid saying. The issue of abortion has been returned to the states, and the Court has offered no directions as to how and when a legislature may choose to protect the child in the womb. The Court has simply decided that nothing in the text of the Constitution, or the legal history of this country, has ever recognized such a right to abortion. As one of my own friends among the justices once put it:

The matter will be sent back to the states and people will be invited to reach their own judgment on how much they value the life of the fetus in the womb. The dissenters take it as a given that the only persons with serious interests at stake here are the women who see their lives and prospects diminished if they are deprived of the chance to order an abortion at a timely moment. What is notably erased from the screen is any recognition of that small creature in the womb, as one who might have the standing of a human being, and whose injuries count.

What the dissenters pretend not to see is that the conservative majority in Dobbs has done nothing to refute that assumption. It has not moved to put in place the rival understanding that the child is indeed a human being with a claim to be protected by the law from its first moments. Justice Alito was quite crisp in pointing out that the test of viability made little sense here. Whether a child sprung from the womb has a decent chance of being sustained outside the womb may be an interesting question in incubator science, but it has no bearing on whether the child has ceased being anything other than a human being at any stages of the pregnancy. Alito came the closest, though, to insisting on that claim of the child to the protection of the law even at its earliest moment: The legitimate interests of the state in regulating abortion could tenably encompass, as he said, a respect for and preservation of prenatal life at all stages of development. But he evidently felt constrained from saying what James Wilson said in the first days of the Constitution. Wilson, one of the premier minds among the American founders, asked this question: If we have natural rights, when do they begin? And his answer was: They begin as soon as we begin to be. And so as he wrote:

For all we can tell, that sense of things was decisively rejected by Alitos colleague Justice Brett Kavanaugh in his morally curious claim that the Constitution is neutral on abortion: On the one side, he wrote, many pro-choice advocates forcefully argue that the ability to obtain an abortion is critically important for womens personal and professional lives, and for womens health. . . . On the other side, many pro-life advocates forcefully argue that a fetus is a human life. In other words, on this construction, a conservative jurisprudence on abortion must begin with the axiom that there is no truth to be known on the human standing of that child in the womb. But that is a jurisprudence that accepts, as its grounding, a radical falsehood. Whatever else it is, it cannot be a coherent jurisprudence.

Justice Kavanaugh is a thoughtful man, and some of us hope that he is willing to take a sober, second look at what he has put in place here. He catches the sense of the holding here: The Court will pronounce no truth on the human standing of that child in the womb, nothing that must provide the predicate for anything that will be legislated in the states. This grave matter, returned to the states, will be argued over in the domain of beliefs and value judgments, with no fixed truths on when human life begins. But in that case, we should not be surprised to discover people in the pro-life states complaining that they have been dispossessed of a deep personal right simply because it wasnt supported by the opinions and beliefs of 51 percent of the people around them.

It is a good thing that this first step has been taken, and the paths of persuasion and argument have opened again. There can be no question that the Court, over the past fifty years, has been the chief engine in changing the culture of this country on abortion. It did not merely pronounce a legal judgment; it tutored the country on the moral rightness of abortion, and the rightful sense of grievance for anyone deprived of that right. And so it becomes apt to ask just what rival teaching the Court will be putting in place now for our people as it sends the matter back to the states. We can be grateful for the decision in Dobbs, but if the American people come to absorb now the notion that the standing of human life bears no objective truth, that the respect for that life depends on the vagaries of opinions whirling aroundus, we can earnestly wonder how the Court is reshaping for the better the sensibilities of people who will be filling this landscape all around us.

And so again, this is the end of the beginning, and now the work begins anew.

Hadley Arkes is the Ney Professor of Jurisprudence Emeritus at Amherst College and the Founder/Director of the James Wilson Institute on Natural Rights & the American Founding in Washington, D.C.

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The End of the Beginning of the End of Abortion | Hadley Arkes - First Things

Embryology

Widower wins right to have baby using embryo created with his late wife – The Guardian

A 38-year-old widower has won a landmark legal case giving him the right to have a baby with a surrogate using the last remaining embryo created with his late wife.

Ted Jennings and his wife, Fern-Marie Choya, had spent years trying to have children and had sought fertility treatment, but Choya died suddenly while pregnant with twin girls in 2019. The fertility regulator, the Human Fertilisation and Embryology Authority (HFEA), rejected Jenningss request to be able to use their last frozen embryo to start a family because Choya had not given written consent for posthumous surrogacy.

But on Wednesday, the high courts family division ruled that Jennings can use the embryo, in what could be the UKs first case of posthumous surrogacy. The couple had not been given adequate opportunity to consent to this scenario, the court found, in a judgment that will put pressure on the HFEA to review consent procedures.

In her judgment, Mrs Justice Theis, a family division judge, said: I am satisfied that, in the circumstances of this case, the court can infer from all the available evidence that Ms Choya would have consented to Mr Jennings being able to use their partner-created embryo in treatment with a surrogate in the event of her death. This is being considered in the context where, in my judgment, she had not been given relevant information and/or a sufficient opportunity to discuss it with the clinic.

The couple, both originally from Trinidad, met in London and married in 2009. After five years of fertility treatment and two miscarriages following ectopic pregnancies, they conceived in 2018 and were expecting twin girls. But 18 weeks into her pregnancy, Choya suffered a severe pregnancy complication and died, aged 40.

The couple had given consent to the embryos being used in the event of Jenningss death, the court heart in evidence last month, but Choya was not asked the equivalent question. Instead, her form stated that she should seek more information from the clinic if you wish your eggs or embryos to be used in someone elses treatment if you die. The court ruled that it was far from clear how this related to posthumous surrogacy and suggested that the HFEA may want to consider whether the form should be reviewed in order to provide the clarity required and avoid this situation occurring again.

James Lawford Davies, Jenningss lawyer and a partner at the firm Hill Dickinson, said: I am delighted that the court has found in Teds favour and that he can now proceed with surrogacy treatment. It was clear that this is what Fern would have wanted and this very thorough judgment allows her wishes to be respected.

In a statement, the HFEA said: This is a tragic case and the HFEA continues to have every sympathy for Mr Jennings. The act of parliament which governs fertility and embryology in the UK is clear that signed written consent is always required in such cases. The risk today is that this decision will undermine that position, and diminish the protection it gives to a persons express wishes about the use of their embryos after their death. We will carefully consider the judgment before deciding whether to appeal.

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Widower wins right to have baby using embryo created with his late wife - The Guardian