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A Conceivable Idea

Ova banks—a process and technique of freezing human ovum (eggs) for future use has finally come in India, courtesy Mumbai's Lilavati Hospital. Sonal Shukla takes a look at the possibilities for women offered through this concept

The IVF lab in Lilavati Hospital is planning to introduce seperate liquid nitrogen containers for HIV positive patients

A recent World Health Organisation survey indicates that there are roughly 20 million infertile couples in India. In another case, it was noticed that although the success rate for in-vitro fertilisation (IVF) is 20-25 per cent, it is only 10 to 12 per cent for intra cytoplasmic sperm injection (ICSI). Considering these figures, it is the need of the hour to have an ova bank that can allow women to postpone motherhood at a later date or offer solutions for women struggling with reproductive problems. As an answer to this, Lilavati Hospital, in 2006, started the first ever ova bank in India.

This will now allow women to freeze their eggs and utilise as per their wish. Moreover, Dr Hrishikesh Pai, Gynaecologist and Infertility Consultant and Head of the IVF Centre of the Hospital alongwith Dr Nandita Palshetkar, Consultant Gynaecologist at Lilavati, have launched the first ovarian tissue bank in the country in association with Dr Claus Anderson, who has established an ovarian bank in Copenhagen with frozen 240 ovaries. This has brought a ray of hope to women facing the grim prospect of cancer at an early age whose gonadal function is threatened by treatments—yet aspire to have a family.

"Until a year-and-a-half ago, the concept of egg freezing and the pregnancies following that were minimal" - Dr Hrishikesh Pai Gynaecologist, Infertility Consultant Head of the IVF Centre Lilavati Hospital, Mumbai

Dr Pai says, "Biotechnology is advancing by leaps and bounds and we wanted to bring in cutting-edge technologies to support the existing unit. Moreover, with patients opting for preventive medicine, we realised the potential of such a
concept." Little wonder why Lilavati left no stone unturned to import the ova bank technology from Denmark and Japan.

Last year, the hospital introduced oocyte freezing technology and, recently, the ovarian cortical tissue freezing technology, especially for women with cancer was introduced. "While the earlier technique can be used for egg donation, this cannot be said for the latter one. Both these technologies are a part of our IVF centre, says Dr Pai.

"Ovarian tissue banking avoids ovarian stimulation and provides opportunity for preserving gonadal function in pre-pubertal as well as adult patients. This technique is also an option for women wanting to conceive her own genetic child, but does not anticipate starting a family at an early age," explains Dr Palshetkar.

According to Dr Pai, until a year-and-a-half ago, the concept of egg freezing and the pregnancies following that were minimal. But with breakthroughs in the vitrification technology, increasing number of units worldwide is able to produce positive results. Interestingly, the Seoul-headquartered DNA Ovum Bank claims to be Asia's first and largest human egg bank in the business.

Oocyte Freezing

"Ovarian tissue banking avoids ovarian stimulation and provides opportunity for preserving gonadal function in pre-pubertal as well as adult patients" - Dr Nandita Palshetkar Consultant Gynaecologist Lilavati Hospital Mumbai

Though the applications of both the technologies are different, they share a common thread. In the oocyte freezing technology, also known as egg freezing, the patient is given a hormone injection for 10-11 days after the routine investigation, so as to produce a good amount of eggs (around 10-15). The procedure takes about 20 minutes, is done under general anaesthesia and the patient is discharged after three hours. The eggs are dissected and prepared for freezing (exposed to the cryoprotectants and then vitrified). The dissected eggs are then frozen in the straw. Temperatures are gradually dropped at the rate of 0.3 degrees centigrade every minute and the eggs are kept in liquid nitrogen containers at -196 degrees
centigrade (slow freezing technique). This minimises the damage that can be caused to the eggs. The temperature makes the ovum extremely inactive, and can be preserved for centuries. The nitrogen level is checked every four days and maintained. Four months later, the donor is tested for HIV. If the tests are negative, then the quarantined eggs are thawed and used. Precautions are taken to ensure the eggs are totally free from the possibility of transmitting HIV. Two types of donors—voluntary and shared—assist the ova bank in helping infertile couples. It is important that the voluntary donor is in the 21-33 year age group, and married with children.

Ovarian Cortical Tissue Freezing

This is a boon for women (under 40) diagnosed with some form of invasive cancer. Most female cancer patients of reproductive age do not have an alternative to employ established assisted reproductive technologies to safeguard their fertility. This technology has one drawback, though. Patients need to wait for two to six weeks to get the eggs out, in which time the cancer is likely to progress. "Instead of using the oocyte freezing, we can use the ovarian cortical tissue freezing for such patients, provided the cancer specialist allows us four to six weeks to do so," explains Dr Pai.

The ovary is removed from the patient and the tissue carefully dissected with microsurgery; small pieces/strips of the ovary with thickness of one mm are cut and added to the cryopreservant media in vials. All of a woman's eggs can be found in the outer layer (cortex) of the ovary, while the inside is a pulp of blood vessels with no specific function except to provide nutrition to the eggs and follicles situated on the periphery. It is further put through a computer controlled, gradual freezing process. The tissue pieces are then thawed and transplanted back into the woman once she has recovered, or wants to resume fertility. Still at an experimental stage worldwide, this procedure has led to three births since 2004 - a baby girl in Belgium, another one in Israel and a pair of twins in the US.

Different Strokes

So who can avail of such treatments? Women with premature ovarian failure, ineffective ovaries post-ovarian surgery, post-chemotherapy, premature menopause, repeat failure with in-vitro fertilisation and menopausal patients who have lost their children and want another can avail the facilities of the bank. When the Hospital started the oocyte freezing technology, it was first utilised for egg donation programme. The usage of ovarian cortical tissue technology for cancer patients is also catching up. The Hospital already has got three patients, of which one patient is already being operated.

As egg freezing is already a commercially established phenomenon, the procedure of oocyte technique costs around Rs one lakh, not counting the Rs 10,000 each year for maintenance. The overian cortical tissue freezing technology is still a philanthropic effort as the technology is at a quasi experimental phase.

According to Dr Duru Shah, Obstetrician and Gynaecologist affiliated with the Breach Candy Hospital, Mumbai, "Pregnancy with oocyte freezing still needs experimentation, and women seeking to freeze their eggs for lifestyle purpose should be told about the chances. This is because conception rates are much lower than with the natural option of pregnancy. However, cortical freezing technology is a good option for women with cancer." Dr Anirudh Malpani, Infertility Specialist from Mumbai, agrees, "Every technology needs to withstand the test of time; here both the technologies are not clinically mature enough. According to ASRM guidelines, although the techniques hold promise for fertility preservation, lack of sufficient data on success rates and safety issues means these procedures should be performed experimentally under Institutional Review Board guidelines, and only in women who face potentially sterilising treatment."

The official (ASRM) American Society for Reproductive Medicine Practice Committee Guidelines published in 2006 states: "Likewise, ovarian transplantation procedures should only be performed as experimental procedures in centres under institutional review board (IRB) guidelines. These procedures (either ovarian tissue cryopreservation or transplantation) should not be advertised as established clinical services offered by assisted reproduction programmes. Appropriate current experimental indications primarily focus on providing an alternative for women who immediately face near term medical therapies that clearly threaten their future fertility. Due to the present potential risk-to-benefit ratio, ovarian tissue cyopreservation should not be currently either marketed or offered as a means to defer reproductive aging.

Ovarian Tissue Bank—Denmark

Lilavati Hospital has launched the first ovarian tissue bank in the country in association with Dr Claus Yding Andersen, professor at Laboratory of Reproductive Biology, University Hospital of Copenhagen, Denmark. The Hospital acquired the technology of ovarian cortical tissue freezing from Dr Copenhagen's centre which has till date cryopreserved ovarian tissue from more than 240 women in Denmark. Ovarian tissue banking avoids ovarian stimulation and provides opportunity for preserving gonadal function in pre-pubertal, as well as adult patients. While talking about the technology, Dr Copenhagen says, "We cryopreserve the cortical strips of the ovary. In the cortical strips resting follicles each contain one oocyte. The follicle supports the oocyte during growth but is also the main factory of oestradiol (female sex hormones). Thus, not only is the fertility potential preserved but also the capacity to produce endogenous oestrogens." It is the only centre in Denmark performing the procedure, but the recovery of ovarian tissue is done in several hospitals around Denmark. These hospitals then transport the tissue to the centre. The centre has now obtained EU-approval and is inspected by a legal Danish body similar to the US FDA for performing this procedure. Says Dr Chopenhagen, "As there are 70 cases in Denmark annually (five million inhabitants) you can calculate the number of cases that could be performed in India and the number of cases and indications for cryopreserving will only increase."

The Approach

An appropriate is an important aspect to make this a success, feels the experts working in the IVF centre of Lilavati. Thorough counselling is given to patients prior to the investigation. "We let them know about the success rate. As the technology used for the cancer patients is still in its experimental stage, we let them know in advance," explains Dr Pai. "For oocyte freezing, in case of Lilavati's own egg donation programme, we have patients lined up, but we are yet to see more cancer patients and those opting for lifestyle freezing purpose," says Dr Pai.

Moreover, it is important to remember that it requires a certain amount of expertise to handle such projects. Experts warn that plain investments are not what is required alone. Skills include handling of eggs correctly, the type of kits and culture media and freezing chemical used, and so on. When Lilavati Hospital took the decision to start the ova bank, Dr Pai was sent to Tokyo, while Dr Palshetkar went to Copenhagen to learn about the technologies. Moreover, the Hospital follows a rigorous screening procedure to avoid HIV transmission, while the IVF centre follows (GLP) Good Laboratory Practices. It is also planning to introduce separate liquid nitrogen containers only for HIV positive patients.

Dr Pai believes that sustaining the IVF unit as a whole is a matter of concern as it is a skill-based procedure and requires a lot of experience, as it can enhance increased rate of pregnancies. The secret of sustenance of ova bank depends on the good recovery of oocyte, assurance of pregnancy and patient turnover. The IVF centre has a good technical background and patient turnover which comes through constant communication with GPs, specialists and the general masses.

sonal.shukla@expressindia.com