Minimum ovarian stimulation involving combined clomiphene citrate and estradiol treatment for in vitro fertilization of Bologna-criteria poor ovarian responders

Abstract

Aim: The aim of this study was to assess the efficacy of a minimal ovarian stimulation involving combined clomiphene citrate (CC) and estradiol (E2) administration for poor responders with diminished ovarian reserve (DOR).

Material and methods: In this case-control study, we recruited 41 consecutive hypergonadotropic poor responders (69 cycles) who met Bologna-criteria and had experienced cancellation of oocyte retrieval. In 10 (20 cycles), 11 (21 cycles) and 20 patients (28 cycles) between 2012 and 2014, follicular development was induced using an E2 cycle, CC cycle and CC + E2 cycle, respectively. After confirmation of high follicle-stimulating hormone levels (15-40 mIU/ml) at menstrual day 3, DOR patients were treated with oral E2 of 1.0 mg/day, CC of 100 mg/day, or both CC and E2 continuously, until ovulation induction. Two days later, we transvaginally aspirated the follicles, performed in vitro fertilization, and cryopreserved the cleavage embryos. One warmed embryo was transferred into the uterus during the hormone replacement cycles.

Results: For the E2, CC, and CC + E2 cycles, the median patient age was 41 years in all groups, and the serum anti-Müllerian hormone levels were 0.2 ± 0.3, 0.4 ± 0.4, and 0.2 ± 0.3 ng/mL, respectively (P = 0.258); follicular development failure rates were 50.0%, 19.0%, and 3.6%, respectively (P < 0.001); numbers of retrieved oocytes (/cycle) were 0.5 ± 0.6, 0.8 ± 0.7, and 1.2 ± 1.1, respectively (P = 0.033); and clinical pregnancy rates (/cycle) were 5.0%, 4.8%, and 10.7%, respectively (P = 0.725).

Conclusion: CC + E2 administration for the patients with DOR was effective with a lower cancellation rate of oocyte retrieval and a higher number of retrieved oocytes.

Keywords: clomiphene citrate; diminished ovarian reserve; estrogen replacement; in vitro fertilization; minimal ovarian stimulation.