Test Tube Babies >>
Dr. I.N. Hinduja
Consultant Gynaecologist and Obstetrician, KEM Hospital, Mumbai

Infertility affects 15-20% couples attempting conception. Some of these may not respond to the regular fertility enhancement protocols. It is in these patients that getting gametes together under observation may serve the purpose and this goal accompanied with sophisticated technology culminated in the birth of Louise Brown in 1978. Since the birth of this first test tube baby, Assisted Reproductive Technologies (ARTs) have flourished and thousands of children have been born.

The technique wherein the female gamete i.e. oocyte or egg is manipulated is called ART. Assisted reproductive technologies are specialized treatment modalities and include In Vitro Fertilization and Embryo transfer (IVF-ET); Gamete Intra Fallopian Transfer (GIFT); Zygote Intra Fallopian Transfer (ZIFT), Intracytoplasmic Sperm Injection (ICSI), Assisted Hatching, use of donor oocyte and embryo, cryo preservation and Prenatal Genetic Diagnosis (PGD).

Women with absent or blocked tubes, severe endometriosis, a hostile cervical factor require ART. Couples with unexplained infertility, or male factor infertility with poor sperm count and quality, and patients with immunologic factors are also candidates for ART. Males or females with genetic disorders likely to be transmitted to the offspring or progeny, benefit from ART with oocyte or sperm donation. The scope of ART has expanded beyond the usual definition of infertility to include premenopausal women and those with premature ovarian failure with donor oocyte, gestational surrogates for women without a functional uterus, and fetomaternal incompatibilities such as severe Rh sensitization or maternal chemotherapy.

The preliminary requirements are:
  • Vaginal and cervical infections if any are treated.
  • Laparoscopy and hysteroscopy is done to confirm indication, accessibility of ovaries and fallopian tubes as also the assessment of uterine cavity.
  • Semen Analysis
  • Counselling regarding schedule, cost, success rates and risks involved.

What is Ovulation Induction?

In a physiological cycle only one dominant follicle is there with subsequent release of a single egg. Although the world's first test tube baby was born in a natural cycle, but to optimize a couple's chances of conception, controlled ovarian hyperstimulation is done. There are various drugs like Clomiphene citrate, gonadotrophins and gonadotrophin releasing hormone (GnRH) agonists to induce formation and release of more than one egg. Successful pregnancy rates after embryo transfer are directly related to the number of embryos transferred.

After giving the requisite drugs the cycle is monitored with hormonal assays and serial sonography to measure growth of follicle is assessed. When a mature follicle of size 17-18 mm is seen oocyte retrieval is planned 36 hours after giving Human Chorionic Gonadotrophin (HCG). Oocyte retrieval requires hospitalisation for a couple of hours and is done under ultrasonographic control with short anaesthesia.

For the sperms, a fresh or frozen semen sample is used and processed by swim up technique and other methods to improve and optimize the quality of sperm.

Getting the gametes together

Actual insemination is done 4-6 hours after retrieval. Immature oocyte are incubated in vitro for 24 hours to achieve maturation. Fertilization is checked 18 hours after insemination. Presence of 2 pronuclei is indicative of fertilization. Embryo transfer (ET) is done either 48 hours after fertilization or 5 days after oocyte retrieval (at a blastocyst stage). This method has a success rate of 42-45%. The woman is kept flat on her back for 4 hours after ET. The luteal phase in supported by supplementation of hormone Progesterone. Excessive embryos can be cryopreserved or used for embryo donation. Serum beta-HCG levels are done on 14th day after ET. To avoid multiple pregnancy, not more than 3 embryos are transferred in one cycle.

Gamete Intra Fallopian transfer (GIFT) i.e. transfer of both gametes into the ampullary portion of the fallopian tubes should give better pregnancy rates than IVF-ET. As this technique is invasive and requires at least one functional tube, it is not so widely practiced. After fertilization, when zygotes (two pronuclear stage) are transferred to fallopian tube is known as ZIFT.

Intra Cytoplasmic Sperm Injection (ICSI) is an ART wherein under high magnification the sperm is introduced within the cytoplasm of the egg. If there has been failure of IVF more than twice, those having low sperm count with low motility, and obstructive azoospermia, ICSI can be attempted with sperm collected surgically. Fertilization rate is 72-75%. In these cases pregnancy rate is 45%. Elderly patients having repeated implantation failure may benefit by processing techniques like assisted hatching and partial Zona dissection.

Embryo cryopreservation may decrease the risks and expenses when more than one IVF-ET cycle is required. Surplus embryos can be stored indefinitely in liquid nitrogen and transferred at a later date giving the couple a second chance at pregnancy. The major risks of ART besides the expenses, include ovarian hyperstimulation, repeated hospitalisation, multiple pregnancies and psychological trauma.

Counselling is of major importance considering the schedule, risks and high costs. Such couples usually have a feeling of guilt and inadequacy and failure rates of ART may have great impact on the psychological bearing of the couple. Gestational surrogacy, preimplantation diagnosis with embryo biopsy and embryo cryo-preservation bring medical ethics and law into the picture.

Above all, childless life and adoption should be an available option to couples following repeated failures as only 50% couples benefit from ART.