Question 1

Can you say more about the injectable medications you mentioned for weight loss and obesity management?

Dr. Hrishikesh Pai · Accepted Answer

Three types of weight-loss drug have now arrived: GLP-1 agonists, GLP-1/GIP combinations, and a GLP-1/GIP/glucagon combination that is about to be released. The GLP-1 drug is semaglutide, which has been used in the United States since 2017, where even general practitioners prescribe it; in India the first consultation has to be with a physician. Semaglutide is available orally and by injection. The injection starts at 0.25 mg subcutaneously once a week for the first month and the dose is then increased slowly; the oral form has to be taken daily. It acts on the brain and slows emptying of the stomach, so patients do not feel like eating. Pancreatitis, sudden vision loss and thyroid cancer can occur, but they are very rare. Mounjaro, which is tirzepatide from Eli Lilly (GLP-1 plus GIP), is better from a weight-loss standpoint. It was launched in the United States two years ago at about $1,000 a month and has been released in India at one-sixth of that cost, about Rs 15,000 to 20,000 a month, because the drug matters so much when about 30 percent of people are obese. Exclusivity on semaglutide ends in March, and nearly 11 companies are expected to release it in India in April.

Question 2

The internet is full of claims about Ozempic and similar weight-loss drugs. Do these drugs have serious side effects?

Dr. Hrishikesh Pai · Accepted Answer

Most of it is false information. Excess weight brings heart, kidney, liver and knee-joint problems, psychological problems and urinary problems, and against those the side effects of the drug are very small. Refusing it is like refusing to fly because a plane may fall: complications occur, but rarely. Paracetamol can cause liver failure, yet we still give it to children for fever. Because this is an obesity drug, it has attracted too much attention and hype. Every drug, including blood pressure drugs, has complications; you always have to balance them against the advantages, and here the complications are small compared with the benefits.

Question 3

Does the drug create dependency, so that someone who loses weight once and regains it later has to keep using it?

Dr. Hrishikesh Pai · Accepted Answer

We do not use it in pregnancy. What we do now is give the weight-loss drug and bring the weight down; some people lose 40 kilos or more. Once the weight is down, I stop the drug, start ovarian stimulation, retrieve the eggs, make the embryos and freeze them, and transfer the embryos a month later, so that the drug has been stopped for at least two months before the embryo transfer. The same caution once applied to metformin, which was considered dangerous in pregnancy and is now used throughout pregnancy. Studies of women who became pregnant while on these drugs without knowing it have so far not shown an increase in birth defects, but the data are still limited. We have to be cautious, but not super cautious: losing weight improves longevity, and obesity has to be managed aggressively.

Question 4

For IUI stimulation, what combination of medication do you use (for example, clomiphene plus metformin), and when do you start it?

Dr. Hrishikesh Pai · Accepted Answer

Patients usually reach us after they have already tried clomiphene. For IUI stimulation we give clomiphene 50 mg, two tablets, from day 2 to day 6, and HMG 150 IU on day 7 and day 9. Be careful in PCO patients: I avoid HMG there because it can cause hyperstimulation. Polycystic ovarian morphology is diagnosed on transvaginal ultrasound by more than 15 follicles in an ovary, often in a necklace pattern, and AMH is very important; AMH is our gold-standard test. Do an AMH test for your daughters too, to see whether their ovarian reserve is good. If a daughter is not married between 30 and 35, she should freeze her eggs, because later the egg quality falls and genetic abnormality rises; freezing should happen before 35.

Question 5

If genital tuberculosis is diagnosed, what are the clinical findings in the uterus?

Dr. Hrishikesh Pai · Accepted Answer

Most patients have amenorrhoea or very scanty periods; some present with heavy bleeding. We normally do TB-PCR and D&C with histopathology, but I always like to do a laparoscopy, because the PCR is often falsely negative and the visual diagnosis is very important. Laparoscopy also lets us cut adhesions and burn endometriosis, and if genital tuberculosis is found and anti-tubercular therapy is started, many women become pregnant on their own. If tuberculosis is missed, IVF will not give a pregnancy either. If the patient will not accept laparoscopy, do hysteroscopy, D&C with histopathology, culture, TB-PCR and a chest X-ray; palpate the cervical and groin lymph nodes; take the history and family history; do sputum AFB on three consecutive days, interferon-gamma release assays and a Mantoux test. Often we are not sure, and on a strong suspicion we give anti-tubercular therapy.

Question 6

Once genital tuberculosis is confirmed, how do you plan the management?

Dr. Hrishikesh Pai · Accepted Answer

We give anti-tubercular therapy: AKT-4, four drugs, for two months, followed by AKT-2, two drugs, for the rest of a nine-month course. It must be given properly. Many people give it for only one or two months; the organism then becomes resistant, and multidrug-resistant tuberculosis is a major problem worldwide that kills many patients because treatment was incomplete. Once you start anti-tubercular treatment, whether the diagnosis was right or wrong, do not stop it. After treatment, repeat laparoscopy and hysteroscopy to check that everything is normal, then try IUI, and go to IVF if that fails.

Question 7

Why should we consider IVF over intrauterine insemination, and what are the complications of IVF?

Dr. Hrishikesh Pai · Accepted Answer

WHO recommends a step-by-step approach. First do the tests: rule out anovulation with a day-21 progesterone above 10, rule out tubal block with an X-ray of the womb (HSG), rule out uterine factors with a 2D or 3D ultrasound, take a proper history and do a semen test. If everything is normal, try timed intercourse with clomiphene for 3 to 6 months. If that fails, do IUI: most of us now do three cycles, though six is acceptable, and about 30% of couples become pregnant with IUI. Only then go to IVF. The biggest side effect of IVF is failure to become pregnant, but across three complete cycles nearly 80 to 90% of patients achieve a pregnancy, more in younger women. With advanced freezing, the first cycle usually yields enough embryos to freeze, so later attempts use frozen embryos without repeating the whole cycle. Eighty per cent of patients do not need IVF: with good laparoscopy and hysteroscopy, good ultrasound and a good IUI lab, you can achieve pregnancy for 80% of patients in your own country. Only 20% need IVF.

Question 8

What are the factors that reduce the success rate of IVF?

Dr. Hrishikesh Pai · Accepted Answer

The biggest factor is the age of the patient. IVF registries worldwide, such as SART in the United States and the HFEA in the United Kingdom, report success by age band: under 35 about 40%; 35 to 37 nearly the same, 35 to 40%; 37 to 39 about 25 to 30%; 39 to 41 about 15%; over 41 about 5 to 10%. As age advances, genetic abnormalities in the eggs rise, so embryos form but many are genetically abnormal, and even when pregnancy occurs many end in miscarriage. The other problem is when there are no eggs: poor ovarian reserve, with AMH as low as 0.3 or 0.4. Many of these patients refuse donor eggs, so we offer PRP (platelet-rich plasma) injected under ultrasound or laparoscopic guidance, and stem-cell treatment. At laparoscopy I also rule out genital tuberculosis, which can itself reduce ovarian reserve. I tell these patients plainly that PRP and stem cells do not work and that adoption or egg donation is the better route, but many insist on trying with their own eggs.

Question 9

Most women who come to my clinic with infertility have a white, cheese-like vaginal discharge. Could there be a connection?

Dr. Hrishikesh Pai · Accepted Answer

They have an infection; the cheesy material is a fungal infection. Treat both the husband and the wife, and give lactobacillus. A hanging-drop preparation or culture often misses Trichomonas, Chlamydia or Mycoplasma, so we give everyone a three-drug combination kit of secnidazole, fluconazole and azithromycin, to both husband and wife, together with local clotrimazole cream. Also rule out diabetes: many of these patients are obese and their blood sugars will be high, so treat the diabetes or the obesity and advise on hygiene.

Question 10

A woman with blood group O negative was given anti-D after delivering her first child, and recently miscarried at 16 weeks. How can such couples best be helped?

Dr. Hrishikesh Pai · Accepted Answer

If the antibody titre is very high, it becomes very difficult. If the facility is available, they should go for surrogacy with a surrogate who has no red cell antibodies, because the surrogate will not attack the baby. Iso-immunisation otherwise means intrauterine blood transfusions to the baby, babies with jaundice and kernicterus, and many losses; it is a mess. Surrogacy is the easier way out than repeated attempts, and it is available in many African countries.

Question 11

Is letrozole considered more effective than clomiphene for ovulation stimulation?

Dr. Hrishikesh Pai · Accepted Answer

No. I like clomiphene; it is a master drug. Letrozole is for PCOS patients. In my practice, normal responders (AMH above 2 and below 3.5, antral follicle count 7 to 15) get clomiphene or clomiphene plus HMG, and for IVF I use pure HMG. Poor responders (AMH below 1.5, antral follicle count below 7) again get clomiphene plus HMG. Hyper-responders with PCO (AMH above 3.5, antral follicle count above 15) get letrozole.

Question 12

What is the referral process for sending a patient's case for review?

Accepted Answer

Every referring doctor is assigned a relationship manager who guides the referral. The reports are collected and documented in a case file, which is shared with the Fortis coordinator and then with Dr. Pai's team. A review from Dr. Pai's team comes back within 48 to 72 hours, followed by further guidance.

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