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Overview of Infertility

General information and international perspective

The birth of Louise Brown (the world’s first IVF baby) in 1978 ushered in a new revolution in the treatment of infertility.

IVF and its derivatives in preimplantation diagnosis, stem cells and the ethics of assisted reproduction continue to attract immense attention scientifically and socially. All these topics were introduced by 1970 but yet hardly a day passes without some public recognition of events related to IVF, and clinics spread even further worldwide. Now we must be approaching 2 million IVF births, it is time to celebrate what has been achieved by so many investigators, clinical, scientific and ethical.

IVF primarily dealt with female related infertility for patients with blocked tubes, endometriosis, PCOS and unexplained Infertility. Little could be done for sever male related infertility until the advent of Intra Cytoplasmic Sperm Injection (ICSI), about 20 years ago wherein scientists could actually inject a single sperm into the egg of the wife and produce a baby even with the lowest of sperm counts and worst of sperm motility. It is now possible to extract sperm from the testicles (TESA) in cases of azoospermia (zero sperm counts) and use these for ICSI and help the couple have their own biological child (without the need for sperm donors). Also, for men with blocked vas deferens (the tube that transports sperms from the testicles to the outside) can avail of Percutaneousepididymal sperm aspiration (PESA) with ICSI for the same successful outcome as TESA-ICSI.

The third biggest advance since the introduction of IVF & ICSI has been vitrification (cryo-freezing) of gametes and embryos. Over the past two years there has been a shift towards performing more frozen embryo transfers with better preparation of the uterus resulting in higher take home baby rates. Most clinics with a good vitrification program can now deliver success rates of 50% per IVF cycle as compared to about 35-40% with conventional fresh embryo transfer.

More and more women are opting for higher education and pursuit of their career ambitions. In the bargain, marriage and child bearing are being deferred to a later age. Often, after the age of 37 the egg quality is not the best and many of them have to resort to egg donation, thereby sacrificing their genetic component in the child. These young and dynamic women now have the option of freezing their eggs (saving their fertility “in time”) at a young age for use at a later date thereby making their lives complete both on the career as well as personal front.

A simpler technique called Intrauterine insemination (IUI) has been in existence for a long time and is beneficial for young couples with minor problems or those experiencing sexual dysfunction.

Recently, Preimplantation genetic diagnosis (PGD) has further helped to enhance success rates especially in women over the age of 35 or those with history of miscarriages or abnormal offspring. In this technique, the embryos are biopsied and evaluated in a special genetic laboratory to ensure that only genetically normal embryos are transferred back into the woman.

There is another very important aspect of ART practice and that is third party reproduction which is extremely successful but governed by religious, ethical and legal issues. In India, most of the clinics are compliant with the ART guidelines laid down by the Indian Council of Medical Research for the practice of these techniques. There is sperm donation for men who have total testicular failure and zero sperm counts or for those who cannot afford ICSI. There is egg donation for women who are menopausal or have had multiple IVF failures owing to poor egg quality. And finally, there is gestational surrogacy for women who have had failed multiple cycles of IVF because of problems in the uterus.

On the horizon, we have stem cell treatment for augmenting oocyte and endometrial quality (in women with poor quality eggs or uterus). Also, a fast developing field of epigenetics (DNA contribution from the mother even if there is a donor egg involved) offers renewed hope to many patients who have to opt for a donor egg. Three-parent IVF holds great promise for couples as it would ensure that the genetic component is the mother’s even if she has to take a donor egg for some help with the pregnancy. Intra-ovarian PRP activation also seems promising but we need more data for routine implementation.

The Indian Perspective

In an over populated nation such as ours, the problem of infertility is still a major health problem. As per WHO statistics in 1982, 1 out of every 16 couples was reported to be infertile. Today the figure stands at 1 in 4 couples. In fact, in a recent survey of our major metropolitan cities, the incidence of infertility in the 30 plus age group was found to be 46% (Alarming!!). Late marriage, delayed child bearing, increased use of contraceptives and the increasing incidence of medical disorders such as endometriosis, polycystic ovaries, genital tuberculosis and male sub fertility have all contributed to this increased incidence. Current data suggests that male factor infertility is on the rise. In almost 50% of couples, low sperm count, poor sperm motility and zero sperm count are the prime causes of infertility.

We (Indians) less fertile?

A recent study comparing Spanish and Indian women showed that Indian women have a lower ovarian (egg) reserve than their caucasian counterparts (lower AMH, higher FSH and longer duration of infertility). Also, Indian American women showed a significantly lower Live birth rate with IVF than white American women (24% vs 41%).

Increased maternal and age at marriage, increased number of working women, rising tobacco and alcohol consumption and rising levels of obesity are all contributory. Also, Indian women show a higher incidence of polycystic ovaries and genital tuberculosis as compared to the USA.

Studies have confirmed that South Asian women have a poor egg reserve as compared to Caucasian women, and are likely to suffer from earlier onset of infertility and poorer outcomes from infertility treatment.

Preliminary evaluation of the couple involves a clinical history, examination of the female partner by transvaginal ultrasonography, semen analysis, hormone estimations (Day 2 serum FSH, LH, Prolactin, and TSH) and a diagnostic laparoscopy and hysteroscopy. On completion of the investigations, the diagnosis is established as one of.

Hormonal problems : Failure to produce eggs and irregular menses.

Blocked fallopian tubes : Tuberculosis being a common cause in our country.

Endometriosis : Menstruation occurs inside the body in the ovaries or elsewhere causing cysts and infertility.

Male factor : Low sperm counts, poor sperm motility or zero sperm counts.

Unexplained infertility : Where there is no apparent cause for the infertility.

Conventional Management by medical or surgical means would help approximately 40% of couple to conceive. These would include laparoscopic surgery for fibroids, endometriosis, surgery for opening the fallopian tubes, hysteroscopic surgery for septum, polyps, submucous fibroids and metroplasty for small or T-shaped uterus. In addition, ovulation induction (drugs given to stimulate egg production) with clomiphene citrate and gonadotropins would benefit the women with PCOS or other endocrine anomalies. Correction of associated endocrinopathies such as high prolactin levels or poor thyroid function is also important. Sperm anomalies would require evaluation by a urosurgeon / andrologist and medical or surgical therapy such as varicocele ligation in select cases. For the remaining 60% Assisted Reproductive Technologies have emerged as a great boon over the past three decades. Today, it is possible to retrieve a human oocyte from the ovary, fertilize it outside the body in the laboratory with the husband's sperm and replace it into the uterus for achieving an offspring.

Intrauterine Insemination (IUI)

This entails deposition of washed and capacitated sperm into the uterus at the time of spontaneous or induced ovulation. The indications include borderline male factor infertility such as reduced counts and sperm motility, sexual dysfunction and sperm deposition problems, poor sperm migration in the female genital tract and women with hormonal defects. Some amount of controlled ovarian hyper stimulation is required in the form of clomiphene or gonadotropin injections with hCG being added as the ovulation trigger. Several techniques are available for sperm washing such as layering, double spin or density gradients. The success rate with this procedure is in the range of 10 – 30 % @ indication and 2-3 cycles are generally advocated before proceeding to higher ART forms.

In-Vitro Fertilization and Embryo Transfer (IVF-ET)

The birth of Louise Brown in 1978 (world's first IVF baby) revolutionized the treatment of moderate to severe female factor infertility. This was the original test tube baby procedure wherein the woman is subjected to controlled ovarian hyperstimulation with gonadotropins for obtaining more than one egg (oocyte). We believe in individualised ovarian stimulation and judiciously use the short antagonist vs the long agonist protocol for best outcomes. We do not believe in “one size fits all”. For high responders and patients with PCOS we strictly use the short antagonist protocol with the GnRH agonist trigger to ensure patient safety and totally eliminate the chance of ovarian hyperstimulation syndrome (OHSS). Once the follicles are at the size of 18 mm, hCG / the agonist trigger is administered and the oocytes are aspirated at 36 hours post hCG (before they rupture) and transferred to the IVF laboratory. Here they are cultured in petri dishes containing culture medium. Subsequently, the oocytes are fertilized with the husband's sperm after 4 - 6 hours of incubation. After 16 - 20 hours, the oocytes are checked for the 2 pronuclear stage implying successful fertilization. After another 24 hours of culture, the best 1-2 embryos (4-cell stage) are transferred back to the uterus or frozen and transferred in the subsequent month. In the event of one of them implanting, successful pregnancy is established. The most disappointing event in an IVF cycle is to get a negative pregnancy test and therefore we have a strict policy of NOT transferring poor quality embryos. Rather we encourage the couple to undergo another round of stimulation with a different protocol in order to try and get better quality embryos. Also, in recent times, AMH levels play a predictive role for IVF success. For example, young patients with a normal AMH of 2-5 ng/ml can expect a 50-60% chance of pregnancy, whereas with levels of < 2 ng / ml the success rate would reduce to 20-30% only. Indications for IVF include tubal block, severe endometriosis and PCOD, unexplained infertility and infertility due to any cause refractory to conventional medical and surgical management. Success rates are in the range of 40-50% per cycle and 3 - 5 cycles are recommended before opting for alternate treatment options.

Intracytoplasmic Sperm injection (ICSI)

This technique has been the greatest boon for male factor infertility which does not respond to conventional medical or surgical treatment. With this technique, men with severe oligo or asthenozoospermia can still their own child without taking resort to a semen bank. As with IVF, the wife's oocytes are aspirated. On a special microscope with a micromanipulator, a single sperm is picked up in fine microneedle and injected manually into the oocyte. Embryos are transferred fresh or frozen as per the IVF doctor’s decision. The couple can expect a 40-50 % chance of conception per cycle. For azoospermic men with an obstructive pathology (eg: Congenital absence of vas deferens) sperm can be aspirated directly from the epididymis (PESA) and used for ICSI. In addition, for azoospermic men with a non-obstructive pathology, sperm can be retrieved directly from the testis (TESA) and used for ICSI. Almost miraculously, PESA or TESA with ICSI gives the same results as with ejaculated sperm (50 % per cycle). We also offer Micro TESA (surgical aspiration of sperm under microscopic control) with cases of primary testicular failure and azoospermia.

Oocyte Donation

Women who are menopausal or suffering from premature ovarian failure and amenorrhoea can now hope to become mothers with the application of oocyte donation and IVF. Here, the uterus is prepared for conception with estrogen / progesterone priming. Once suitable oocytes are available, IVF is performed with the husband's sperm and the embryos transfered to the recipient. 60 % pregnancy rates per cycle can be expected with this technique.This technique is also of immense value to patients with repeated IVF failures owing to poor ovarian reserve (low AMH or high FSH levels) as well as poor or suboptimal egg quality leading to multiple IVF failures.

Therapeutic Insemination With Donor Sperm (TID)

Where finance is an issue, patients suffering from severe male factor infertility who cannot afford ICSI or patients with primary testicular failure who do not have sperm even with TESA can opt for donor sperm from a semen bank. This remains one of the oldest ART methods known to mankind. The success rate of IUI using donor sperm is 35% per cycle.

Embryo Donation

In the event of the wife being menopausal and the husband being azoospermic, the infertile couple can still hope for a pregnancy with embryo donation. This helps fulfil the biological desire of a woman to be a mother Vis a Vis adoption. It also helps certain patients with repeated miscarriages or repeated IVF failures. The success rate with embryo donation is 70% in the presence of a normal endometrium.


In cases of end organ failure, such as for example uterine damage owing to genital tuberculosis, the couple can hope to have their own genetic offspring by IVF with transfer of the embryos to a surrogate mother who carries the child for nine months and then hands over the baby to the biological parents. The success rate with own eggs is 40% and with donor eggs is 70%. As per current government regulations, surrogacy is only available for couples where both partners are Indian citizens. Currently, the procedure is not available for OCI or PIO status individuals

Facts, Not Myths

Most cases of PCOD benefit with currently available ovulation inducing agents. IVF remains a promising option for resistant cases of anovulatory infertility. Cases of genital tuberculosis with tubal damage and a normal uterus are excellent candidates for conception with IVF. Stage III and IV endometriosis patients are benefited with IVF. Most cases of severe oligo or astheno- zoospermia can expect to have their own biological child with ICSI.Azoospermic men with some sperm production in the testes can hope to father their own child with PESA or TESA with ICSI Menopausal women can expect to conceive with success rates on par with younger women with the technique of oocyte donation and IVF.

Important Counselling After Cycle Failure

Please remember that success rates in the best IVF centers in the world are in the range of 50% per started cycle. It is important for the patient to remember that the cumulative success rate after 3 cycles of IVF is in the range of 80 %. This is an important statistic that highlights the need to do repeated cycles.

Dr Jatin is always available for counselling after a failed cycle. It is important to have this discussion to understand the gravity of the problem. Often, the first cycle reveals problems of oocyte (egg quality) or fertilization failure, problems with embryo development or the endometrial lining which need to be discussed and solved.

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