hCG supplementation may stimulate intrafollicular estradiol, androgens in IVF patients
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In patients undergoing in vitro fertilization, higher doses of human chorionic gonadotropin supplementation have a considerable effect on stimulating the intrafollicular levels of estradiol and androgens, with a propensity toward a more androgen-dominated environment, according to data from a randomized trial.
Researchers from Denmark and Belgium conducted the prospective, dose-response study at the Fertility Clinic at Copenhagen University Hospital. They evaluated 62 patients scheduled for in vitro fertilization (IVF) aged 25 to 37 years, with normal BMI and regular menstrual cycles. Patients were placed on a gonadotropin-releasing hormone agonist regimen with recombinant follicle-stimulating hormone 150 IU/day and randomly assigned from the date of stimulation (stimulation day 1) to receive human chorionic gonadotropin (hCG) supplementation as follows: dose 0, 0 IU/day; dose 50, 50 IU/day; dose 100, 100 IU/day; and dose 150, 150 IU/day. The researchers analyzed the hormone concentrations of the follicular fluids in respect to treatment groups, sizes of follicles and embryo quality.
According to findings, in large follicles, supplementation with hCG nearly tripled the concentration of estradiol — dose 0: 1,496 nmol/L; dose 50: 3,138 nmol/L; dose 100: 4,338 nmol/L; dose 150: 4,009 nmol/L (P<.001) — tripled the concentration of androstenedione and yielded a fivefold increase in testosterone — dose 0: 15 nmol/L, dose 50: 38 nmol/L, dose 100: 72 nmol/L; dose 150: 56 nmol/L (P<.001). The ratio of estradiol to testosterone was reduced sharply, with this ratio reaching its lowest at dose 100 and the highest at dose 0. Significantly higher progesterone levels were seen in large follicles that yielded high-quality embryos compared with small follicles producing poor-quality embryos. Large follicles that yielded high-quality embryos also had significantly higher estradiol to testosterone, estradiol to androstenedione, and progesterone to estradiol ratios vs. smaller follicles yielding poor-quality embryos.
“The estrogen to androgen ratio being highest in large follicles with oocytes giving rise to good-quality embryos confirms the importance of the follicle’s capacity for aromatization to produce good quality oocytes,” researchers wrote. “Based on biochemical evidence and embryological observations, we conclude that in terms of clinical efficacy and safety, introduction of hCG supplementation up to a daily dose of 100 IU could be proposed.”
Disclosure: The researchers report no relevant financial disclosures.