Low-dosage clomiphene reduces premature ovulation rates and increases transfer rates in natural-cycle IVF

Abstract

Natural-cycle IVF has been suggested as an alternative IVF treatment. However, efficacy is limited due to high premature ovulation rates, resulting in low transfer rates. This study investigates whether low dosages of clomiphene citrate reduce premature ovulation rate and increase transfer rate. Of 112 women included (aged 35.2 ± 4.5 years) 108 underwent one natural-cycle IVF cycle with human chorionic gonadotrophin (HCG) to induce ovulation and 103 underwent one natural-cycle IVF cycle with 25 mg/day clomiphene from about day 7 until HCG administration. Before retrieval, 1.2 monitoring consultations per cycle were required. Clomiphene reduced premature ovulation rate, from 27.8% without to 6.8% with clomiphene (P < 0.001) and increased transfer rate from 39.8% to 54.4% (P = 0.039). Clinical pregnancy rates without and with clomiphene were 27.9% versus 25.0% per transfer and 11.1% versus 13.6% per initiated cycle. Use of clomiphene resulted in mild hot flushes and headache in 5% of patients. Nausea and persisting ovarian cyst formation was not observed. In conclusion, clomiphene citrate led to very few side effects, required 1.2 monitoring consultations, significantly reduced premature ovulation rate and significantly increased transfer rate per initiated cycle, an effect which was not age dependent.

Serum but not follicular fluid cytokine levels are increased in stimulated versus natural cycle IVF: a multiplexed assay study

“…Thus, exogenous stimulation with gonadotropins, as widely practiced in current procedures of in vitro fertilisation for the induction of a multifollicular reaction, has many effects on the follicular mechanism and growth, not only triggering multiple follicle growth but also possibly negatively affecting follicular and oocyte function. Studies with naturally matured follicles have indeed shown that the implantation potential of oocytes obtained from natural cycle IVF (NC-IVF) follicles is higher than of those from conventionally gonadotropin stimulated (c-IVF) follicles (Aanesen et al, 2010;Gordon et al, 2013;Von Wolff et al, 2014b). Furthermore, a recent study from our laboratory has revealed that the follicular endocrinological milieu was significantly altered by conventional IVF stimulation protocols (Von Wolff et al, 2014a), suggesting that the exogenous stimulation affects follicular function.…”

Treatment‐related psychological stress in different in vitro fertilization therapies with and without gonadotropin stimulation

“…Further exclusion criteria for the study participation were current psychological treatment, serious psychiatric illness and insufficient knowledge of German. The women were counseled in accordance with our study results described elsewhere . These studies revealed that treatment time to achieve a pregnancy is 30% longer in NC‐IVF, whereas costs per achieved pregnancy are 30% lower.…”

“…The influence of these factors on the mental state of the couple and thus their psychological stress has largely been unstudied in detail up to now. Advances in IVF treatments without gonadotropin stimulation, NC‐IVF now represents an alternative form of treatment where pregnancy takes longer to occur but the success rate is good overall . Furthermore, the costs per pregnancy are lower , with injections, anesthesia for oocyte collection and embryo selection not being required .…”

“…NC‐IVF patients received no stimulation at all or very low dosages of clomifene citrate (25 mg orally per day) from day 6 or 7 of the menstrual cycle until the day of ovulation induction to reduce the risk of premature ovulation as described elsewhere . One consultation took place around days 10–12 [15 min, transvaginal ultrasound and serum analysis of luteinizing hormone (LH) and E2)].…”

“…A prospective longitudinal study was therefore carried out, in which the psychological burden of cIVF and three consecutive NC‐IVF treatments in an unselected sample of fertility treatment patients was measured before and during as well as after IVF treatment. The two arms of the study were chosen in this form, as cIVF with transfer and three NC‐IVF treatments lead to a similar cumulative pregnancy chance and a similar number of consultations .…”