Ovulation Induction: What the Drugs Do and What to Expect

What ovulation induction is for

Ovulation induction is medication given to make ovulation happen, or happen more predictably, in someone whose ovaries are not releasing an egg reliably. That is a narrower purpose than the phrase "fertility drugs" suggests. If you are ovulating regularly, inducing ovulation does not give you a second egg-release each month or shorten the time to conception, and NICE is explicit that ovarian stimulation should not be offered as a stand-alone treatment for unexplained fertility problems.

So the first step is not a prescription. It is establishing whether ovulation is happening at all, and if not, why. NICE recommends a mid-luteal serum progesterone blood test — day 21 of a 28-day cycle — to confirm ovulation even where cycles are regular, with later and repeated testing where cycles are long or irregular. Where cycles are irregular, serum gonadotrophins should also be offered.

Why the cause decides the drug

Ovulatory disorders are grouped by where the problem originates, and the treatments are not interchangeable. NICE Clinical Knowledge Summaries describe three World Health Organization groups: hypothalamic-pituitary failure (around 10% of women with infertility), dysfunction of the hypothalamic-pituitary-ovarian axis (around 85%, of which PCOS is the largest part), and ovarian failure (around 4–5%). Treating the wrong group is not a near miss; it is a treatment that cannot work.

Hypogonadotropic hypogonadism

NICE recommends gonadotrophins with luteinising hormone activity, or gonadotrophin releasing hormone, to induce ovulation in this group. It also advises that people in this group who have a BMI under 18.5, or who undertake high levels of exercise, may improve their chance of regular ovulation, conception and an uncomplicated pregnancy by increasing body weight towards a healthy range or moderating exercise levels. That is a specific recommendation for a specific diagnosis, not general lifestyle advice.

High prolactin

Where an ovulatory disorder is caused by hyperprolactinaemia, NICE recommends cabergoline. Bromocriptine is the other drug used for this purpose. Both work by reducing prolactin production, which allows ovulation to return.

PCOS

NICE has removed its PCOS recommendations from NG257 because it is developing a separate guideline on polycystic ovary syndrome. In practice, clomifene citrate is often the first drug used in this group, and the HFEA notes it can also be used by people with late or irregular periods. Letrozole is also used for ovulation induction in PCOS. Metformin, which is not strictly a fertility drug, is sometimes used where insulin resistance is part of the picture. Because the guideline is under development, this is an area to discuss with a specialist rather than to settle from a webpage.

None of these drugs is named here with a dose, and that is deliberate. Dose, duration and escalation are individual clinical decisions, and the HFEA's advice is unambiguous: only take medication under the care of a specialist, and fertility drugs will only work if you have been correctly diagnosed and are taking the right medication for that diagnosis.

Monitoring is the safety mechanism

The risk that makes ovulation induction a specialist treatment rather than a prescription is producing too many follicles. NICE gives two recommendations that belong together:

• Inform people offered ovulation induction with gonadotrophins about the risk of multiple pregnancy and ovarian hyperstimulation before treatment starts.
• Use ovarian ultrasound monitoring to measure follicular size and number as an integral part of gonadotrophin therapy, to reduce the risk of multiple pregnancy and ovarian hyperstimulation.

The HFEA makes the same point about clomifene: there is a risk of developing too many follicles, which could result in a multiple birth carrying serious health risks to both the pregnant person and the babies, which is why it strongly recommends taking it only under the supervision of a fertility specialist. Ovarian hyperstimulation syndrome, associated particularly with gonadotrophins, can in rare cases be fatal.

This is the reason to be sceptical of clomifene bought online or prescribed without scanning. The drug is not the hard part. The monitoring is.

Side effects, and what to report

Many people taking fertility drugs feel fine. The HFEA lists reactions to tell your clinic about, including stomach pain or bloating, hot flushes, breathing difficulty, mood swings, heavy periods, breast tenderness, insomnia, increased urination, spots, headaches, weight gain, dizziness and vaginal dryness. Breathing difficulty and marked abdominal swelling are the ones to raise urgently rather than at your next appointment, because of the overstimulation risk.

If the drugs do not work

The HFEA's answer here is a list rather than a next drug, because what follows depends on why the treatment did not succeed, if a reason can be found. Options include IVF, ICSI, IUI or surrogacy, and in some situations using donated eggs, sperm or embryos. That is a change of approach rather than a longer course of the same medication, which is why several unmonitored cycles of the same drug is a pattern worth questioning.

It is also worth knowing that the drugs used in ovulation induction are prescription-only in the UK, with the exception of antioxidants and vitamins, and that the HFEA recommends being treated by a specialist at a licensed clinic so that the right medication is prescribed and you are moved on to alternatives at the appropriate point.

What ovulation induction cannot do

It does not treat blocked tubes, and NICE recommends tubal assessment before donor insemination where the history suggests tubal damage. It does not treat male factor problems, which NICE Clinical Knowledge Summaries put at around 30% of couples, with problems in both partners in about 40%. It does not improve egg quality. And it is not a treatment for unexplained infertility on its own: for unexplained fertility problems after two years, NICE recommends discussing either up to four cycles of IUI with ovarian stimulation using gonadotrophins, or IVF.

If ovulation induction is offered without a confirmed ovulatory diagnosis, ask what is being treated and how it was established. And if the drugs do not work, the next step depends on why, which is a conversation about your diagnosis rather than about trying the same thing for longer.