Obstetrics & Gynaecology/Ovulation inductionlow yield

Ovulation induction agents

also: letrozole · clomifene · gonadotrophins · fertility drugs

Overview

Drugs to induce ovulation in anovulatory infertility (esp. PCOS). Letrozole is now the preferred first-line agent; gonadotrophins are used in assisted conception.

Mechanism

Letrozole (aromatase inhibitor) lowers oestrogen → reduced negative feedback → ↑FSH → follicular growth. Clomifene (a SERM) blocks hypothalamic oestrogen receptors → ↑GnRH → ↑FSH/LH. Metformin improves insulin sensitivity (PCOS adjunct). Gonadotrophins (FSH ± LH) directly stimulate the ovary; hCG triggers ovulation.

Indications

Anovulatory infertility (PCOS)
Controlled ovarian stimulation in assisted conception

The agents

Letrozolearomatase inhibitor

oral, days 2–6

Now preferred first-line in PCOS (higher ovulation + live-birth vs clomifene; ESHRE/international guideline).

ClomifeneSERM

oral, days 2–6

Long-standing option; multiple-pregnancy + OHSS risk; limit cycles.

Metformininsulin sensitiser

oral

PCOS adjunct (cross-references the diabetes card).

Gonadotrophins (FSH/hCG)injectable

SC, monitored

Assisted conception; OHSS risk — needs monitoring.

Adverse effects

Multiple pregnancyserious

Clomifene/gonadotrophins.

Ovarian hyperstimulation syndrome (OHSS)serious

Gonadotrophins > clomifene; ascites, third-spacing, VTE.

Clomifene: hot flushes, visual disturbance, anti-oestrogenic thin endometriumcommon

Letrozole: hot flushes, fatigue (well tolerated)common

Cautions & contraindications

Liver disease (clomifene)all

Ovarian cysts / hormone-dependent tumourall

Pregnancy (these are pre-conception agents)pregnancy

Interactions

Monitoring & kinetics

Ultrasound follicle tracking; mid-luteal progesterone to confirm ovulation,Counsel re multiple pregnancy + OHSS

Oral agents early follicular phase; gonadotrophins are monitored SC injections.

Source: NICE CG156 — Fertility · ESHRE — PCOS 2023 (letrozole 1st-line)