Use of Clomiphene Citrate in minimal stimulation in vitro fertilization negatively impacts endometrial thickness: an argument for a freeze-all approach.

Beverly G Reed,Laurice Bou Nemer,Bruce R Carr,Orhan Bukulmez,John L Wu

doi:10.5935/1518-0557.20180070

Beverly G Reed, Laurice Bou Nemer + Show 3 more

Open Access

https://doi.org/10.5935/1518-0557.20180070

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Abstract

ObjectiveMinimal stimulation IVF is a treatment option that uses clomiphene citrate (CC). We sought to evaluate how CC impacts endometrial thickness during minimal stimulation IVF cycles.MethodsWe retrospectively analyzed a cohort of 230 cycles in 119 poor ovarian response patients. The IVF cycles were studied in three groups: 130 minimal stimulation cycles, 29 mild stimulation cycles, and 30 conventional high dose gonadotropin releasing hormone (GnRH) antagonist cycles. Thirty-three minimal stimulation IVF patients had 41 frozen embryo transfers (FET) which allowed us to study whether the CC effects were prolonged.ResultsEndometrial thickness in the minimal stimulation group was significantly lower than the mild and conventional stimulation groups (7.3±2.2mm versus 11.4±3.3mm versus 12.9±3.8mm, respectively, p<0.0001). In patients who underwent minimal stimulation IVF followed by FET, significantly thicker endometrial thickness was achieved during their FET cycles as compared to their minimal stimulation cycles (7.95±2.1mm versus 10.3±1.8mm, p<0.0001).ConclusionWe concluded that endometrial thickness is impacted during minimal stimulation IVF cycles. Since negative effects on endometrial thickness are not observed in the patients’ subsequent FET cycle, a freeze-all approach is justified to mitigate adverse endometrial effects of CC in minimal stimulation IVF cycles.

Highlights

Minimal stimulation in vitro fertilization (IVF) is an alternative to conventional high dose controlled ovarian stimulation (COS) for patients with diminished ovarian reserve or for expected poor responders
There are studies that have been performed on intrauterine insemination (IUI) cycles that indicate clomiphene citrate (CC) may have a detrimental effect on the endometrial stripe (ES) thickness and pattern (Dehbashi et al, 2003; Haritha & Rajagopalan, 2003; Nakamura et al, 1997)
The peak ES thickness per cycle in the minimal stimulation group was significantly lower than the high dose gonadotropin group or the mild stimulation group (7.3±2.2mm vs. 12.9±3.8mm vs. 11.4±3.3mm, respectively, p

Summary

Introduction

Minimal stimulation in vitro fertilization (IVF) is an alternative to conventional high dose controlled ovarian stimulation (COS) for patients with diminished ovarian reserve or for expected poor responders. A commonly prescribed minimal ovarian stimulation protocol uses daily clomiphene citrate (CC) and a small amount of gonadotropin on days 5, 7, and 9 of the ovarian stimulation (Figure 1) (Reed et al, 2015). Clomiphene citrate (CC) is a selective estrogen receptor modulator. The increased amounts of FSH allow for ovarian stimulation with lower doses of gonadotropin than would be traditionally used during an IVF cycle. There are no studies evaluating the effect of CC on the endometrium during IVF stimulation. The negative impact of CC on the endometrium during IVF with prolonged CC use deserves further scrutiny

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Conclusion