Absolute uterine factor infertility

“... the womb is the field of generation; and if this field be corrupted it is in vain to expect any fruit though it be ever so well sown.” Aristotle

Absolute uterine factor infertility poses an immense challenge to reproduction since the uterus plays a pivotal role in embryo implantation and foetal sustenance. Absolute uterine factor infertility affects approximately one in 500 women of childbearing age, or 1.5 million women worldwide.[¹]The main reasons for absolute uterine infertility are the congenital absence of the uterus (Mayer-Rokitansky-Küster-Hauser syndrome), surgical removal or complete damage of the endometrial lining (Asherman’s syndrome) due to infections, radiation exposure or extensive curettage.

The incidence of uterine congenital anomalies is 3% to 13% in the infertile population and 0.5% in the general population. Mayer-Rokitansky-Küster-Hauser syndrome is seen in 1 per 4,500 women which accounts for less than 3% of all müllerian malformations. Surgical removal of the uterus may be performed for gynaecological cancers, benign uterine diseases commonly multiple fibroids, adenomyosis or dysfunctional uterine bleeding and complications associated with pregnancy and delivery. Hysterectomies for uterine rupture, atony, or placenta accreta and percreta are performed in approximately 1 per 5,000 deliveries.[²]

What can we offer these women to fulfil their desire for motherhood? Currently, the options available for treatment are mainly experimental – uterine transplant and an artificial uterus. Gestational surrogacy remains the only feasible route though it is fraught with problems – complicated surgery, government regulations and an enormous expense being the major issues.

UTERINE TRANSPLANT

The first successful uterine transplantation was performed by Brannstorm and colleagues (2014) in a patient with MRKH syndrome. In their series of nine patients, the uterus was taken from related live donors in the age group of 32–62 years. Successful uterine transplantations have also been reported from India and other countries. Uterine transplant is extremely challenging as it involves removing the uterus from the donor along with its vascular supply (uterine and ovarian vessels), a procedure that can take up to 12–14 hours, followed immediately by transplantation into the recipient. Re-establishment of the uterine vascular supply is critical to success. Subsequently, patients need to be on immunosuppressants till such time that they complete their family, to prevent graft rejection and finally the uterus has to be removed after delivery or even earlier in the event of complications Ironically surgical time for the recipient is significantly shorter than that for the donor. Uterus from deceased donors can also be used[³] however sourcing such organs and an adequate evaluation prior to transplantation, poses a problem. Pregnancy has to be achieved through IVF and an increased risk of ante-natal and neonatal complications has been reported. If the procedure becomes available outside a research protocol the cost will be enormous. Regulations also need to be put in place to ensure safety of the donor.

ARTIFICIAL UTERUS

An artificial uterus is a device that permits an extracorporeal pregnancy. The ability to create an artificial environment for implantation and foetal development in vitro would be the last frontier in assisted reproduction technology. Research on complete ectogenesis has been going on since 2002. Epithelial and stromal cells layered on matrigel support have been used to form the endometrial lining and implantation has been achieved. Legislation has so far prohibited embryo growth outside the body beyond 6–14 days. United kingdom and several other countries have formalized this rule. Research for developing an artificial uterus using stem cells and scaffolding is in progress. In 2017 ‘The children’s Hospital of Philadelphia’ reported success with partial ectogenesis using a plastic bag called “the bio-bag” that contained synthetic amniotic fluid, they were able to support foetal development in lamb. A ‘bio bag’ consists of a sealed plastic bag, a pumpless oxygenator circuit, and an umbilical cord access enabling the constant exchange of amniotic fluid, water and nutrients. The umbilical cord is cannulated with an artificial circulation mimicking the function of a normal placenta.[⁴] This technology may help to save babies born with extreme prematurity. Whether these technologies can go from bench to bedside remains to be seen. Ethical concerns relating to unforeseen damage to the developing foetus, undermining sexual equality and abortion rights for women are being raised.

SURROGACY

Gestational surrogacy is a boon for women with absolute uterine factor infertility. These women get to use the healthy womb of another woman to carry their child. A gestational surrogate has no genetic connect to the baby since pregnancy is achieved by transferring an embryo of the intending parents. There is much ethical debate around surrogacy, and regulations that govern its use vary from country to country. While some countries like the United States allow commercial surrogacy, others like France prohibit surrogacy altogether. International cross-border surrogacy has become hugely popular, with Ukraine and Georgia being the largest hubs because of lower costs. India too was a popular country for surrogacy prior to government regulations banning surrogacy for foreign nationals.

In India, gestational surrogacy is allowed only for Indian nationals and people of Indian origin whilst traditional surrogacy is prohibited. Exploitation of the economically weak and misuse of surrogacy for monetary gains have spurred activists to protest against commercial surrogacy. Subsequent to these complaints, India brought out regulations to improve the safety of surrogates and to make the process of surrogacy less exploitative. Unfortunately, neither of the two aims has been achieved. Though gestational surrogacy is legal in India it has to be altruistic – a utopian concept in today’s age of commercialization!

The Surrogacy (Regulation) Act, 2021 was enacted by parliament and became effective on 25^th January 2022 after notification in the Official Gazette by the Union Government. Instead of giving clarity, the act has created unprecedented confusion and inequity, in addition to infringing on the reproductive rights of individuals. The act allows only married or divorced women to avail of surrogacy leaving out single women who wish to become mothers and the LGBT community. Multiple clearances and affidavits are required from government and legal cells exposing the woman’s medical condition to many prying and insensitive eyes. The need for doctor-patient confidentiality has been completely disregarded. This total invasion of privacy adds to a woman’s emotional distress. The financial requirements have increased as well, even though the surrogate is not to be given any compensation. Thus this bill has created an atmosphere ripe for corruption.

In conclusion, at present, the only feasible option for women with an absolute uterine factor is gestational surrogacy in countries which permit it. Where surrogacy is not permitted women must adopt if they wish to experience motherhood. Uterine transplantation is a complex surgical procedure requiring organ donation and subsequently IVF for achieving a pregnancy. Cost is prohibitive and only a privileged few would be able to avail of the procedure. Though research for developing an artificial uterus is ongoing, time will tell when and if it will be available. Regulations on surrogacy should take into consideration that women take this route out of necessity, not of choice. Rules need to be made to mitigate their pain.

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Conflicts of interest

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