Ovulation Induction: What It Is, Why You Need It

Ovulation induction means using medication to make an ovary release an egg in a woman who is not reliably releasing one on her own. It is one of the oldest fertility treatments there is, one of the cheapest, and by a distance the most effective thing available for the commonest treatable cause of infertility in India.

It is also frequently done badly — started without checking whether the woman is actually anovulatory, run without monitoring, continued for a year when it plainly is not working, or given with the drug that the evidence now says is second choice.

First: are you actually ovulating?

This sounds obvious and it is where the whole thing goes wrong most often.

The strongest single clue is your cycle. Periods arriving regularly, at broadly the same interval each month, usually mean you are ovulating. Cycles that come every 45 days, or every three months, or unpredictably, usually mean you are not — or not every month.

• Mid-luteal progesterone. A blood test taken about seven days before your next period is due — day 21 in a 28-day cycle, but later if your cycles are longer, which is exactly where it is usually mistimed. A good level confirms ovulation happened that cycle.
• Follicular monitoring. A series of scans across the cycle showing a follicle growing and then collapsing. The most direct evidence there is, and the same tool used to run a treated cycle.
• Ovulation predictor kits. Useful for timing, unreliable for diagnosis. In PCOS in particular they throw up repeated false positives, because the underlying hormone that they detect runs high anyway.
• Basal body temperature charts. They tell you an egg was released after it is too late to do anything about it, and they drive people slightly mad. Not recommended as a plan.

Why PCOS is behind most of it

Polycystic ovary syndrome is the single commonest cause of anovulatory infertility. The mechanism is worth understanding, because it explains why the treatment works.

In a normal cycle, a group of small follicles begins to grow each month, one becomes dominant, and the rest fade. In PCOS, a much larger group of follicles starts, but the hormonal environment never lets one pull ahead. The ovary ends up holding a ring of small follicles that never matured — which is what the scan report describes — and no egg is released. The lining keeps thickening without the progesterone that would normally shed it, which is why the periods that do come are often heavy and late.

Ovulation induction interrupts exactly this. It does not add eggs and it does not fix the syndrome. It gives the ovary a stronger signal for a few days, so that one follicle can get ahead of the pack.

The other reasons a woman does not ovulate

These are checked before treatment, because some of them are corrected by treating the cause rather than by inducing ovulation at all.

• Thyroid disease. An underactive thyroid disrupts ovulation and is corrected with a tablet. A great many women labelled infertile simply need their thyroid treated.
• High prolactin. Suppresses ovulation, has its own specific treatment, and can occasionally signal a pituitary problem that needs looking at.
• Low body weight, heavy exercise or severe stress. The brain switches off the reproductive signal. Restoring weight and reducing the load restores cycles more reliably than any drug, and inducing ovulation in a significantly underweight woman is not a good idea in any case.
• Obesity. Independently disrupts ovulation, and also makes ovulation induction less likely to work at the standard dose.
• Declining ovarian reserve or early ovarian insufficiency. Here the problem is not the signal but the supply, and ovulation induction is largely beside the point. Our page on AMH and ovarian reserve covers what that number does and does not mean.

What must be checked before you start

Letrozole or clomiphene?

For decades clomiphene citrate was the automatic first choice. That has changed, and the reason is a single large trial that most patients have never heard of.

Seven hundred and fifty women with PCOS were randomly assigned to letrozole or clomiphene for up to five cycles. Live births occurred in 27.5% of the letrozole group against 19.1% of the clomiphene group (p=0.007). Ovulation rates were higher with letrozole too. There was no significant difference between the drugs in congenital anomalies, in pregnancy loss, or in twin pregnancy. Side effects differed rather than favouring one drug outright: fewer hot flushes with letrozole, but more fatigue and dizziness.

Roughly speaking, about twelve women need to be treated with letrozole rather than clomiphene for one additional live birth. That is a large effect for a change that costs nothing and involves no extra procedure, and it is why current international guidance on PCOS places letrozole first.

Letrozole is licensed principally as a breast cancer drug, and its use for ovulation induction is well-established and evidence-based rather than experimental. Women occasionally find this alarming when they read the packet. It is worth knowing in advance, and worth asking about rather than stopping the tablets.

How a treated cycle actually runs

1. Day 2 or 3 of your period — a baseline check, and sometimes a scan to confirm the ovaries are quiet and there is no cyst left from last cycle.
2. Tablets for five days, starting on day 2 or 3, at the lowest dose that is likely to work. Letrozole usually starts at 2.5 mg. The dose is stepped up in later cycles only if the ovary did not respond.
3. Follicular monitoring from around day 9 to 12 — scans every two or three days, watching a follicle grow. This tells you whether the dose worked, how many follicles are growing, and how thick the lining is. These scans are arranged by referral, as are all scans, since we do not run imaging at the clinic.
4. Once a follicle is mature, either a trigger injection is given to release it at a known time, or ovulation is allowed to happen on its own and timed with kits. Whether a trigger is used depends on the cycle and on how the monitoring looks.
5. Timing. Intercourse every day or every other day across the fertile window — the few days leading up to and including ovulation. Every other day is enough; daily is not better, and neither is saving up.
6. Around a week after ovulation, a progesterone level can confirm the egg was released, though once cycles are clearly responding this is often dropped.
7. A pregnancy test roughly two weeks after ovulation, not before. Early tests generate false hope and false grief in equal measure.

Monitoring matters most in the first treated cycle. Once a woman has shown that a particular dose produces one good follicle, later cycles can often be run with less scanning — which is a reasonable conversation to have rather than an automatic downgrade.

How many cycles, and when to stop

Most pregnancies from ovulation induction happen in the first three to four ovulatory cycles. Six is a widely used ceiling. Beyond that, repeating the same treatment with the same result is not persistence, it is drift.

Two different situations get confused here, and they lead to different next steps:

• You are not ovulating on the tablets at all. The dose goes up, or the drug changes. If several cycles at increasing doses produce nothing, that is resistance, and it has its own set of options.
• You are ovulating well but not conceiving. The treatment is working and something else is the problem. This is the point to go back to the tubes, the sperm and the rest of the assessment rather than to add another cycle.

If the tablets do not work

• Weight loss, where weight is a factor. Unglamorous and genuinely powerful in PCOS — a modest reduction restores spontaneous ovulation in a meaningful proportion of women and improves the response in those who still need tablets.
• Metformin. Not a fertility drug in itself, but useful in PCOS with insulin resistance, and sometimes added to a tablet cycle in women who have not responded.
• Gonadotropin injections. Direct stimulation of the ovary. More effective, and requiring proper monitoring, because the risks of multiple pregnancy and overstimulation are real at this level.
• Laparoscopic ovarian drilling. A keyhole procedure on the ovary for resistant PCOS, done at hospital. It restores ovulation in a good proportion of women without the multiple-pregnancy risk of injections, and its effect is not permanent.
• IUI or IVF. Where there is an additional factor, where the tubes or the sperm are the problem, or where several good ovulatory cycles have not produced a pregnancy.

The risks, honestly

• Multiple pregnancy. The main one. With tablets the twin rate is raised but modest — in the trial above, letrozole and clomiphene did not differ. With injections it is considerably higher. Monitoring exists partly to spot a cycle where too many follicles have grown, so that it can be abandoned rather than triggered. If it does happen, our page on twin pregnancy care covers what that pregnancy involves.
• Ovarian hyperstimulation. Rare with tablets, a genuine concern with injections, particularly in women with PCOS who have a lot of small follicles waiting. Severe abdominal swelling, rapid weight gain or breathlessness after a stimulated cycle needs to be seen the same day.
• Ovarian cysts. Usually simple, usually resolving on their own, and the reason for a baseline scan before the next cycle.
• Side effects. Hot flushes, mood swings, headaches and bloating with clomiphene; fatigue and dizziness rather more often with letrozole. Visual disturbance with clomiphene is uncommon and is a reason to stop and ring.
• Ectopic pregnancy. Slightly commoner in any treated cycle. Pain on one side with a positive test needs urgent assessment — see ectopic pregnancy.
• Cancer risk. The long-running worry about fertility drugs and ovarian cancer has not been borne out by the larger studies. It is a fair question to ask and the honest answer is reassuring.

What ovulation induction will not do

It will not improve egg quality, and it will not compensate for age. It will not make a normally ovulating woman more fertile. It will not open a blocked tube or improve a sperm count. And it does not cure PCOS — the syndrome is still there between cycles, and after you have finished having children the metabolic side of it still deserves attention.

What happens at the clinic

Consultation, the full fertility assessment, blood tests, prescribing and managing ovulation induction cycles, adjusting doses, going through your reports and deciding when the plan should change all happen at the clinic. Follicular monitoring scans, like all scans, are arranged by referral — we do not run imaging here, and the scan results are reviewed with you at the clinic. Hysteroscopy, laparoscopy and any surgical step are hospital procedures.

If you have irregular cycles and have been trying for a while, or you have been on the same tablets for a year with nobody scanning you, that is a consultation worth having.