Clinical trial or therapy? India does not have any rules for uterus transplants yet

This week, two women will undergo surgeries that have never been performed in India before. The women, who have medical conditions that have prevented them from getting pregnant, will get transplanted uteruses donated by their mothers . Only a handful of uterus transplants have been performed in the world and all the successful surgeries have been in Sweden. In September 2014, the first baby was born to a woman who got a transplanted uterus.

While India has regulations for organ transplants in general, there are no specific rules for uterus transplants – procedures that are still considered experimental and elective and are not life-saving, necessary surgeries. This has left the medical community divided about Indian doctors undertaking the procedure.

Dr Shailesh Puntambekar, medical director of the Galaxy Care Hospital in Pune, is leading a team of doctors in performing the two uterus transplants this week. Puntambekar is a cancer surgeon who has not performed gynaecological or transplant surgeries before. He became interested in uterus transplants after hearing Dr Mats Brannstrom – a Swedish surgeon who has been the only one to conduct successful uterus transplants so far – give a lecture about it while he was in the United States of America. Six babies have been born to women on whom Brannstrom has performed uterus transplants and two of his patients are pregnant currently.

As a surgeon who has operated on many cervical cancers, Puntambekar feels he is surgically more skilled than gynaecologists to perform a uterus transplant and is going to attempt to “harvest” the donor uterus laparoscopically.

Under whose medical authority?

Puntambekar has got permission from the Maharashtra health department to conduct the surgeries.

Under the Transplantation of Human Organs Act, a state government committee evaluates and grants permission for kidney, liver and heart transplants from donors not related to the recipient. If the donor and recipient are related, a committee at the hospital where the transplant is supposed to take place evaluates the case to ensure that the organ donation is taking place free of pressure or coercion.

The health department director Dr Satish Pawar considers uterus transplants to be like any other organ transplant and said that permissions for the procedure fall within the jurisdiction of the state health department. But, as Puntambekar pointed out: “Until, we applied for permission, the application form did not mention uterus.”

Pawar said that after receiving the application from Galaxy Care hospital, he instituted a committee, which he said closely looked into the details of the two cases and permitted the team to go ahead with the transplants.

“More than the surgery, we are worried about the implications the surgery will have on society,” he said. “There are lot of questions – who decides when the uterus should be removed following the transplant, in case the woman is unable to conceive?”

He said that the government will closely monitor the cases.

Puntambekar, who is a cancer surgeon and has never performed a transplant before, does not think that the first uterus transplants need to be conducted as clinical trials because the end goal is known – for a woman to have a biological child whose gestation takes place in her body

“You do a clinical trial when you don’t know (the outcomes),” he said.

In medicine, clinical trials are conducted to explore whether a medical strategy, treatment, or device is safe and effective for humans. The fact that so few uterus transplants have been performed means that there is not enough evidence as to the efficacy of the procedure and the various circumstances under which it may fail or be unsafe.

“The question is whether informed consent is taken since it is a rare procedure,” said Dr Sanjay Nagral, a transplant surgeon and the publisher of the Indian Journal of Medical Ethics.

Proper informed consent for a uterus transplant might involve informing the patient that there is a small but definite risk of dying and also mentioning other options to have children like surrogacy and adoption, said Nagral.

However, even if women consent, Nagral said that, as a surgeon, he would not do such a procedure. “I recognise that women are often doing this out of societal and family pressures and not necessarily out of her own volition. And therefore the informed consent may also actually not be an independent decision.”

The National Organ and Tissue Transplant Organisation set up under the aegis of the health ministry not only coordinates organ recovery, distribution of organs across India but also lays down guidelines and protocols selection of donors and rules for organ allocation from donated cadaveric organs. The organisation’s director Dr Vimal Bhandari said that health is a state subject and so, permissions acquired from the local authorities for procedures like uterus transplants are valid. “The matter has not been officially referred to me,” he said reserving his comments on the specific details of the cases.

Meanwhile, fertility specialist Dr Kamini Rao of Milann Clinic in Bengaluru is planning to perform uterus transplants in June and will do so in consultation with Brannstrom. She has sought and received permission from the Indian Council of Medical Research to conduct two transplants as part of a clinical trial.

The Indian Council of Medical Research itself has no clear guidelines for the procedure. However, the council’s head Dr Soumya Swaminathan said that doctors should be cautious while undertaking the surgery for which protocols are still being established. She emphasised the need for informed consent from patients who are opting to try the procedure.

The Directorate of Medical Education has compiled a list of organs and tissues that can be transplanted that does not mention the uterus. It is unclear if the Medical Council of India does not have any guidelines on new and experimental procedures.

The ambiguity about permissions has led Brannstrom to withdraw from consulting on the Pune surgeries with Puntambekar. “It is dangerous for these doctors to go ahead with the surgery,” said Brannstrom. “I withdrew after I learnt they don’t have the clinical research agency’s permission.”

Experimental, not therapy

Even before doctors have performed a single uterus transplant, both Puntambekar and Rao have lists of couples who have shown interest in the procedure. Eleven women at the Pune hospital and 31 women at the Bengaluru clinic are ready to opt for uterine transplants, the doctors said.

At present, doctors all over the globe classify uterine transplant as an experimental procedure, including Dr Mats Brannstrom who has performed the only successful uterus transplants to far.

Said Nagral: “Many developed countries where transplantation is much more advanced have actually done a few & stopped. It would be educative to analyse why they did so.”

One reason, Nagral said was that of the ethics of such of procedure, which was cloudy. “In the Indian scenario where regulation and the ethics discourse is in any case weak and a woman’s free choice is a mirage, this procedure is a huge slippery slope,” he said.

In February last year, the first woman in the US to receive a uterus transplant developed complications two days after the procedure and had to have the organ removed immediately.

Several doctors are not in favour of encouraging uterus transplant as therapy with a view that such surgeries are not necessary and life-saving procedures.

“There is no problem in encouraging research on uterine transplant but I am not sure if we are at the stage where it can be offered as therapy,” said Dr Ashok Anand, head of the gynecology department at Grant Medical College in Mumbai.

Uterus transplants may be offered to women with conditions like Asherman’s syndrome where adhesions on the uterus make it impossible to conceive or Mayer-Rokitansky-Küster-Hauser syndrome where the woman is born without a uterus. A woman may also have a dysfunctional uterus or had her uterus removed due to cancer or other conditions.

Infertility specialist Dr Anjali Malpani said that uterus disorders affect a very small percentage of patients who suffer from infertility. An estimated three to five percent of all infertile couples will benefit from the transplant. “It is encouraging that Indian doctors are taking such bold steps,” she said. “But, I think if the mother is ready to give her uterus, why not make her the surrogate instead?”

Malpani believes that a surrogacy is a far more established and less risky procedure compared to uterus transplants, which involves three major surgeries – harvesting the uterus from the donor, transplantation into the recipient followed by childbirth and a hysterectomy to remove the transplanted uterus so that the patient can be brought off immunosuppressant drugs that might be harmful in the long term.

Dr A Charmila, head of the clinical research committee of the Federation of Obstetric and Gynaecological Society of India, said that guidelines need to be framed for regulating uterine transplants to avoid potential exploitation of donors, as has been documented in cases of in vitro fertilisation and surrogacy.

Who benefits?

Transplants such as of heart and liver are life-saving and without it the patient will die. The same is not the case with uterus transplant, where the goal is to fulfil a woman’s desire to carry a pregnancy and have a child.

“It is all about experiencing motherhood,” Dr Indira Hinduja from Mumbai, one of the pioneers of India’s test tube baby procedure.

“There was very little awareness and no laws (in 1988),” she said, referring to when the first test tube baby was created. “India still does not have a legislation to regulate and monitor the booming infertility industry.” The proposed Assisted Reproductive Technology (regulation) Bill is in the draft stage and has not been tabled in parliament yet.

In fact, a couple wanting a uterus transplant has also approached Hinduja.

However, others still advise caution. “The cost versus benefit is really important,” said a doctor who did not wish to be named. “Here, I see more cost and less benefit for these women.”

This is the second of a two-part series on the first uterus transplants in India. Read the first part here.