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

OBJECTIVE: Minimal 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. METHODS: We 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. RESULTS: Endometrial 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). CONCLUSION: We 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.

Effects of ospemifene on the female reproductive and urinary tracts: translation from preclinical models into clinical evidence.

OBJECTIVE: Treatment of menopausal symptoms by compounds with tissue-selective estrogen agonist/antagonist effects, often called selective estrogen receptor modulators, has been researched as an alternative to the use of estrogen therapy. These structurally diverse molecules elicit tissue-dependent responses in hormone-responsive tissues and organs, exhibiting variations in estrogenic activity in preclinical models of postmenopausal reproductive tissues that may improve postmenopausal women's health (eg, prevention and treatment of breast cancer, osteoporosis, and vulvar and vaginal atrophy). METHODS: This literature review investigates whether preclinical data predicted the clinical effects of ospemifene on female reproductive and urinary tract tissues and compares these findings with the specific vaginal effects of other estrogen receptor agonists/antagonists (tamoxifen, raloxifene, and bazedoxifene) in preclinical and clinical studies. Lasofoxifene, although not currently available, is included because of its unique effects on vaginal tissue. RESULTS: The response of endometrial and vaginal tissues to estrogen receptor agonists/antagonists can be differentiated using transvaginal ultrasound, endometrial histopathology, cytologic examination of vaginal smears, assessment of physical changes in the vagina, and relief of symptoms associated with vulvar and vaginal atrophy (such as dyspareunia). CONCLUSIONS: Available evidence indicates that ospemifene has unique effects on tissue, leading to a favorable long-term profile for the relief of vulvar and vaginal atrophy compared with other estrogen receptor agonists/antagonists (eg, tamoxifen, raloxifene, and bazedoxifene) with no short-term concerns about endometrial safety (based on endometrial hyperplasia, carcinoma, endometrial spotting, and endometrial bleeding).