Polycystic ovarian syndrome
ICD-10 E28.2 · ICD-11 5A80.1

PCOS with Anovulatory Infertility: What to Do When Second-Line Therapy Has Failed

This protocol is for women with polycystic ovarian syndrome who have infertility due to anovulation, with no other infertility factors identified, and in whom second-line ovulation induction therapy has not led to ovulation.

Clinical Scenario

Infertility in the setting of PCOS-related anovulation, with no additional contributing infertility factors. The patient has already progressed through first-line and second-line ovulation induction without success.

Second-Line Failure — Escalation Trigger

Second-line therapy — gonadotrophins with ultrasound monitoring using a low-dose step-up protocol, or laparoscopic ovarian surgery — was completed, but ovulation was not detected. This unmet goal is the indication for moving to the third-line protocol described here.

Third-Line Approach (Partial Overview)

When prior ovulation induction lines have been unsuccessful, a third-line assisted reproductive strategy is the next step. In certain clinical situations, an alternative approach to the standard stimulated cycle may also be considered. Full eligibility criteria, sequencing, and clinical decision points are in the complete protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1016/j.fertnstert.2023.07.025

Letrozole should be the first-line pharmacological treatment for ovulation induction in infertile anovulatory women with PCOS, with no other infertility factors.

In the absence of an absolute indication for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), IVF could be offered in women with PCOS and anovulatory infertility, if first- or second-line ovulation induction therapies have failed.

The use of in vitro maturation (IVM) and ICSI could be considered in women with PCOS as an alternative to a stimulated IVF/ICSI cycle, where an embryo is frozen and replaced in a subsequent embryo transfer cycle, acknowledging there is no risk of ovarian hyperstimulation syndrome, but a lower cumulative live birth rate.

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