Question 1

What is the importance of haemoglobin electrophoresis in evaluating infertility?

Dr. Soma Singh · Accepted Answer

It is used as a screening tool before starting any infertility treatment, whether ovulation induction, IUI or IVF, to know whether the woman carries an abnormal haemoglobin such as haemoglobin S or C, or is a thalassaemia carrier. If she is found to be a carrier, the male partner needs to be evaluated too, because of the inheritance risk: if both partners are thalassaemia minor carriers, for example, there is a 25% chance of a child being thalassaemia major. Couples in this situation may need genetic counselling or pre-implantation genetic testing, screening embryos for these conditions before transfer.

Question 2

A married 28-year-old man has had about two years of painless symptoms with sperm in his urine, mostly at the start of urination, and itching around the pubis without a rash. He has no history of conception, and RPR is negative. How should he be managed?

Dr. Soma Singh · Accepted Answer

Sperm in the urine points to retrograde ejaculation, which usually follows pelvic, perineal or urological surgery, or rarely occurs in diabetes: the ejaculate goes backwards and comes out in the urine. Natural conception is usually not possible while it persists. We give the male partner an alkalinising agent; after ejaculation he passes urine, which we collect and centrifuge to separate the sperm. Depending on the concentration, those sperm can be used for IUI or for IVF with ICSI. Any epididymal infection should first be treated with antibiotics, and once it has cleared, the sperm collected from the urine can be used for IUI or ICSI.

Question 3

What is the principle behind the management of oligospermia?

Dr. Soma Singh · Accepted Answer

It depends on how low the concentration is. If it is very low, the man must be genetically evaluated with karyotyping and Y-chromosome microdeletion testing. Correct modifiable lifestyle factors such as smoking and alcohol, and give antioxidants. The rule of thumb is to repeat an abnormal semen analysis after about 8 to 12 weeks, because sperm production takes about 74 days and transport another 15 to 16 days, so the effect shows after about 90 days. If genetic testing is normal and the count improves, you can try medical treatment with IUI. If it does not improve, go to assisted reproductive technology. In short: correct what can be corrected, rule out genetic causes, give medical treatment for at least three months and then reassess.

Question 4

Is there a therapy for azoospermia?

Dr. Soma Singh · Accepted Answer

Do a full hormonal evaluation to establish whether it is hypergonadotropic or hypogonadotropic hypogonadism. Hypogonadotropic hypogonadism can be managed medically with gonadotropins. A hypergonadotropic picture means testicular failure; then sperm retrieval techniques such as TESA or TESE, including microscopic micro-TESE in non-obstructive azoospermia, are used, and the retrieved sperm is used for ICSI to achieve pregnancy.

Question 5

Can you clarify the relationship between ovulation, menstruation and conception?

Dr. Soma Singh · Accepted Answer

In a natural cycle, a cohort of follicles starts to grow under the influence of FSH, but only the most FSH-sensitive one becomes dominant and ovulates while the rest undergo atrophy. After ovulation, the corpus luteum releases progesterone, fertilization takes place in the fallopian tube, and around the fourth or fifth day the resulting embryo enters the uterine cavity, implanting a few days later. Through the same cycle, estrogen from the growing follicle has been building up the endometrial lining in preparation. If pregnancy does not occur, that lining sheds, and that shedding is menstruation. Menstruation happens precisely because pregnancy has not occurred; if it has, the lining is not shed.

Question 6

Given that couples are increasingly delaying pregnancy, how should a woman in her late 30s or 40s think about her real chances, and what can medically be done for her?

Dr. Soma Singh · Accepted Answer

Ovarian reserve varies between women of the same age, so at 40 the number of eggs is not always the problem; quality is. As age advances, meiotic spindle dysfunction makes chromosomally abnormal eggs more likely, and abnormal eggs mean abnormal embryos that either fail to implant or miscarry. The miscarriage risk is around 12 to 15% up to 35, up to about 20% between 35 and 38, 25% between 38 and 41, 50% after 42, and about 95% after 45. A woman keen to use her own eggs can have pre-implantation genetic testing, provided she has enough reserve to grow a day-five blastocyst in the lab; only a genetically normal embryo is then transferred. The endometrium matters too: studies show receptivity declines after 44 even with a donor egg. The biological clock differs from chronological age. Ovarian rejuvenation with platelet-rich plasma injected into the ovaries is being tried; we have started it, and in some women it is found to be useful. It does not reverse ageing; papers are emerging, and more data are needed.

Question 7

So for an older woman it becomes a game of probability: if a healthy egg is retrieved, a blastocyst forms and PGT is normal, can she expect a healthy baby?

Dr. Soma Singh · Accepted Answer

If the egg is healthy and the genetic screening is normal, she might have a healthy baby. But a woman who has tried regularly for 15 or 20 years without conceiving has lower chances, perhaps because of a problem with endometrial receptivity. A woman who only started trying at 41 or 42, with a short duration of infertility, may give surprisingly good results.

Question 8

Even if conception and implantation succeed, age affects the ability to carry a pregnancy. How do you prepare a woman over 35?

Dr. Soma Singh · Accepted Answer

A woman above 35 is of advanced reproductive age, even if young in general terms. Before helping any woman above 35 to conceive, we always screen her medical fitness to carry a pregnancy: liver and kidney function tests, a thorough cardiac check-up, blood sugar, and a Pap smear or LBC to rule out cervical cancer. These are mandatory. Diabetes or hypertension must be controlled before she conceives.

Question 9

What are the complications and risks of embryo transfer?

Dr. Soma Singh · Accepted Answer

The procedure itself has no real complications; what matters is what follows and how many embryos are transferred. Not every embryo implants: the implantation rate is only around 30 to 40%, which is why IVF success is not 100%. To raise the pregnancy rate, more than one embryo is sometimes transferred, two blastocysts or three or four day-two or day-three embryos, and the chance of twins or triplets is then higher than in natural conception. Ectopic risk depends on the skill of the person doing the transfer: placing too many embryos, pushing too much volume or placing them too close to the tube raises it. Heterotopic pregnancy, with one embryo in the uterus and another in the tube, is rare, and is seen with IVF, as are multiple pregnancies.

Question 10

Can IVF be used for women in menopause who still want to conceive, and do they have any extractable eggs at that stage?

Dr. Soma Singh · Accepted Answer

Eggs cannot be retrieved from a menopausal woman, but she can conceive using a donor egg, which is very common and which we do regularly, even in young women. After menopause the ovary no longer produces estrogen, so we give the hormones from outside to prepare the lining, use a donor egg, and these women become pregnant and deliver; there is not a problem, though they need close monitoring.

Question 11

Is there any difference in risk to the baby's health between natural conception and ART?

Dr. Soma Singh · Accepted Answer

The risk is small. The question has been raised since the first IVF baby was born in 1978, more than 46 years ago, and there is no significant increase in congenital anomalies in babies born through ART or IVF; some meta-analyses report a small increase in preterm birth and low birth weight, with the absolute risk remaining low. Much of this relates to the parents rather than the procedure: age, for example a woman above 40 without PGT or an older male partner, and the underlying cause of infertility. The fair comparison is a couple of the same age and fertility conceiving naturally versus through IVF, and there the difference is much smaller.

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