Progesterone Dynamics in Assisted Reproductive Technologies

Progesterone plays a central role in the establishment and maintenance of pregnancy by preparing the endometrium for embryo implantation and sustaining early gestation. In assisted reproductive technologies, supraphysiological hormone levels induced by controlled ovarian stimulation can provoke premature progesterone elevation, leading to endometrial-embryo asynchrony and reduced implantation rates in fresh embryo transfers. Strategies to mitigate this phenomenon include precise monitoring of progesterone during stimulation, adjustment of gonadotrophin regimens, and the adoption of freeze-all protocols when thresholds are exceeded. Recent advances have elucidated the stage-dependent impact of progesterone on day-3 versus day-5 transfers, and responder-specific thresholds have enabled more personalised treatment plans. These insights are reshaping clinical decisions to maximise live birth rates while minimising cycle cancellations and unnecessary interventions globally.

Research from Nature Portfolio

Recent systematic analysis of prospectively collected data indicates that elevated progesterone at the trigger stage is associated with significantly lower live birth and clinical pregnancy rates in cycles with day-3 embryo transfers, whereas outcomes for blastocyst transfers remain largely unaffected. Complementary work distinguished ovarian response groups, demonstrating that low and intermediate responders experience detrimental effects of progesterone rise on live birth rates at defined hormonal cut-offs, while high responders appear less susceptible, underscoring the importance of tailoring protocols to individual ovarian reserve and hormonal profiles.

Progesterone Dynamics in Assisted Reproductive Technologies publication trend

The graph below shows the total number of articles in progesterone dynamics in assisted reproductive technologies across all publications each year (not limited to Nature Index journals).

Technical terms

Controlled ovarian stimulation (COS): Hormonal regimen to induce development of multiple ovarian follicles for assisted reproduction.

Progesterone elevation (PE): Premature rise in serum progesterone during the follicular phase of stimulation.

Endometrial receptivity: Period when the uterine lining is optimally prepared for embryo implantation.

Freeze-all strategy: Policy of cryopreserving all embryos for later transfer to avoid impaired endometrial conditions.

Blastocyst: Embryo development stage around five days after fertilisation, characterised by a fluid-filled cavity and inner cell mass suitable for transfer.

Luteinising hormone (LH): Pituitary hormone that regulates ovulation and progesterone production in the luteal phase.

References

1. hMG addition affects the change in progesterone level during IVF stimulation and LBR: a retrospective cohort study. Reproductive Biology and Endocrinology (2023).
2. Impact of progesterone concentration on human chorionic gonadotropin trigger day on clinical outcomes with one top-quality cleavage-stage embryo or blastocyst transfer in fresh in vitro fertilization cycles. Frontiers in Endocrinology (2023).
3. Progesterone elevation on the day of human chorionic gonadotropin administration adversely affects the outcome of IVF with transferred embryos at different developmental stages. Reproductive Biology and Endocrinology (2015).
4. The slow growing embryo and premature progesterone elevation: compounding factors for embryo-endometrial asynchrony. Human Reproduction (2016).
5. Towards an Improved Understanding of the Effects of Elevated Progesterone Levels on Human Endometrial Receptivity and Oocyte/Embryo Quality during Assisted Reproductive Technologies. Cells (2022).
6. Progesterone elevation on the day of hCG trigger has detrimental effect on live birth rate in low and intermediate ovarian responders, but not in high responders. Scientific Reports (2019).