Can we prevent premature luteinization in IVF cycles?

Area of Science:

• Reproductive Endocrinology and In Vitro Fertilization (IVF)
• Pharmacological interventions in Assisted Reproductive Technology (ART)

Background:

• A long-standing debate exists regarding the negative impact of elevated progesterone levels during ovarian stimulation in IVF cycles.
• Recent meta-analyses involving over 60,000 cycles indicate that a premature increase in progesterone (P4 > 0.8 ng/ml) is associated with reduced pregnancy rates.
• This detrimental effect is hypothesized to stem from impaired endometrial receptivity, as evidenced by the absence of negative impacts on oocyte competence in ovodonation.

Discussion:

• Current strategies to mitigate premature luteinization, such as embryo cryopreservation and deferred transfer to an artificial endometrium, necessitate cycle segmentation and introduce laboratory burdens like potential embryo damage.
• The development of effective pharmacological agents to prevent premature luteinization is highly desirable for routine ART practice.
• Preliminary data and existing literature suggest metformin, administered at 1000-1500 mg daily from the start of monitoring until ovulation triggering, could be a viable option.

Key Insights:

• Premature progesterone elevation in IVF cycles negatively affects pregnancy rates, primarily by impacting endometrial receptivity.
• Metformin shows promise as a preventative treatment for premature luteinization.
• Metformin's potential benefit is suggested to be independent of the patient's ovarian reserve.

Outlook:

• Further clinical validation is required to establish metformin's efficacy and safety in preventing premature luteinization across diverse patient populations.
• Investigating the precise mechanisms by which metformin influences endometrial receptivity warrants further research.
• Successful implementation of metformin could streamline IVF protocols, reduce the need for cycle segmentation, and potentially improve overall ART success rates.