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The early luteal phase administration of estrogen and progesterone does not induce premature luteolysis in normo-ovulatory women

¹ Division of Reproductive Medicine, Department of Obstetrics and Gynecology, ² Department of Public Health and ³ Department of Medicine, Erasmus MC University Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands, ⁴ Center for Reproductive Medicine, Dutch-Speaking Brussels Free University Brussels, Laarbeeklaan 101, 1090, Brussels, Belgium and ⁵ Department of Reproductive Medicine and Gynecology, University Medical Center, Hiedelberglaan 100, 3584 CX, Utrecht, The Netherlands

(Correspondence should be addressed to N G M Beckers; Email: n.beckers{at}erasmusmc.nl)

Objective: The luteal phase after ovarian hyperstimulation for in vitro fertilization (IVF) is insufficient. Therefore, luteal phase supplementation is routinely applied in IVF. It may be postulated that premature luteolysis after ovarian hyperstimulation is due to supraphysiological steroid levels in the early luteal phase. In the present study, high doses of steroids are administered after the LH surge in normo-ovulatory volunteers in order to investigate whether this intervention gives rise to endocrine changes and a shortening of the luteal phase.

Design: Randomized controlled trial.

Methods: Forty non-smoking, normal weight women, between 18 and 37 years of age, with a regular menstrual cycle (24–35 days), received either high dosages of estradiol (E₂), progesterone (P), E₂+P or no medication. Blood sampling was performed every other day from the day of the LH surge until LH+14. Duration of the luteal phase and endocrine profiles were the main study outcomes.

Results: Early luteal phase steroid concentrations achieved by exogenous administration were comparable with levels observed following ovarian hyperstimulation for IVF. No difference in the luteal phase length was observed comparing all groups. However, a significant decrease in LH levels could be observed 6 days after the mid-cycle LH surge (P<0.001) in women receiving P, resulting in accelerated decrease of inhibin A production by the corpus luteum (P=0.001).

Conclusion: The present intervention of high-dose steroid administration shortly after the LH surge failed to induce a premature luteolysis regularly in cyclic women. It seems that the induced transient suppression in LH allowed for a timely recovery of corpus luteum function. Other additional factors may be held responsible for the distinct reduction in luteal phase length observed after ovarian hyperstimulation for IVF.