Clomid, letrozole, gonadotropins: understanding ovarian stimulation before moving on to IVF

Many patients come to the clinic after a year of taking tablets prescribed by a GP or gynaecologist, without a full assessment and without anyone having checked whether ovulation was actually the problem. This is not a criticism of the treatments themselves, which are useful: it is a criticism of their indiscriminate use.

Who is simple ovulation stimulation suitable for?

Ovulation stimulation treats just one thing: the absence or irregularity of ovulation. It therefore makes sense if your cycles are irregular or absent, typically in polycystic ovary syndrome. It serves no purpose if you ovulate normally, except in the context of insemination where the aim is to produce one or two well-timed follicles.

There are two non-negotiable prerequisites: patent fallopian tubes, confirmed by hysterosalpingography or HyFoSy, and a normal semen analysis. Stimulating a woman whose partner has severe oligospermia or whose fallopian tubes are blocked is a waste of time.

Clomiphene citrate

Clomid is the oldest and most commonly prescribed drug. It blocks oestrogen receptors in the pituitary gland, which then increases its production of FSH and triggers follicular growth. It is taken as tablets for five days at the start of the cycle.

It induces ovulation in around 70–80 per cent of women who were not ovulating. Its main drawback is an anti-oestrogenic effect on cervical mucus and the endometrium, which may become thinner. The risk of multiple pregnancy is around 5–8 per cent. After six ovulatory cycles without pregnancy, a change of strategy is required: continuing will no longer be of any benefit.

Letrozole

An aromatase inhibitor, it temporarily lowers oestrogen levels and produces the same pituitary signal, without the adverse effect on the endometrium. In polycystic ovary syndrome, randomised trials have shown a higher live birth rate than with clomiphene. It is now recommended as first-line treatment for this condition by international medical societies, although its use in France remains off-label in certain contexts — a point to discuss with the prescriber.

Injectable gonadotrophins

Recombinant FSH, sometimes combined with LH or hMG, administered as daily subcutaneous injections. These act directly on the ovary, bypassing the pituitary gland. More effective, more expensive, and above all more risky if not monitored by ultrasound: the risk of multiple pregnancy and ovarian hyperstimulation requires close monitoring. They must never be prescribed without monitoring.

When to stop and move on to the next stage

The guidelines I follow, which are shared by most doctors:

• Six ovulatory cycles on clomiphene or letrozole without pregnancy: move on to the next step.
• Three to six inseminations without pregnancy: move on to IVF. Beyond that, success rates plummet.
• Age over 38: shorten all these stages, or even skip them altogether. Time is the most costly factor.
• Low ovarian reserve, damaged fallopian tubes, severe endometriosis or significant male factor: proceed directly to IVF.

The link with treatment abroad

A simple stimulation cycle alone does not justify travelling abroad: it can be carried out very effectively in France, with local monitoring and reimbursement. What drives people to go abroad is what comes next — the delays in egg donation, the age limit, and access to PGT-A. If you’re at the stage of taking tablets, my advice is to first undergo a full assessment and not to rush through the stages unnecessarily. If you’re on your sixth cycle without a clear response, it’s time to seek a structured second opinion.

Frequently asked questions

Source: https://fertilitegrece.com/en/blog/ovulation-induction-clomid-letrozole/ — Triada Baloukoudis, IVF patient coordination in Greece. General information, not medical or legal advice. Printed on

Triada Baloukoudis
Independent IVF patient coordinator in Thessaloniki, with 24 years of experience supporting patients travelling from abroad. More · Contact · Facebook