Predictors of successful conception in a clinical trial of 30 patients with primary amenorrheic hypogonadotrophic hypogonadism treated by ovulation induction

ABSTRACT

A clinical trial was designed to assess the association between the treatment of infertile females with Hypogonadotrophic Hypogonadism and their fertility state considering conception as the desired outcome. Serum hormones, LH, FSH and estradiol, endometrial thickness and count of active ovarian follicles were assessed by U/S to evaluat their role in anticipating a successful conception. Standard protocols of ovulation induction were used in a clinical trial [historical cohort design] of 30 patients with primary hypogonadotrophic hypogonadism. For ethical reasons no attempt was made to fix the number of induction courses given to the female patient [such a variability is suspected to confound the result to a limited extent], so a female was followed up with several courses of ovulation induction [according to the advice of the physician in charge] for a median duration of I year with conception as the final outcome of interest. Four serum hormonal markers [FSH, LH, Prolaction and estradiol] were assessed before and 12-14 days after initiating therapy. Transvaginal U/S was done to measure endometrial thickness and the number of dominant follicles in both ovaries after 12-14 days of treatment. Serum estradiol concentration, endometrial thickness and number of dominant follicles were significant predictors of successful conception. Using endometrial thickness as a decision rule to predict successful conception at a cutoff value of 7 mm, considering the rule as positive if equal or greater than 7 mm, resulted in a positive predictive value [PPV] of 50% [Relative risk of having conception was 4.3 times]. The confidence in a positive rule was increased to 71.4% [PPV =11.4%] when the cutoff value was set higher at 8 mm endometrial thickness. Using the number of dominant follicles as a decision rule at a cutoff value of 4 resulted in a PPV of 60%. This PPV was further increased to 72.7%] when the cutoff value was set higher at 5. An U/S finding of 5 or more dominant follicles increased the.probability of having conception by 12.6 times. A serum estradiol concentration at day 12 of 114 pgm/ml and higher predicted successful conception with a PPV of 50% [relative risk of having conception was 7], increasing this cutoff value of serum estradiol to a maximum of 498.5 pgm/ml increased the PPV to 66.7%. a clinician can predict successful conception after the first 2 weeks of initiating therapy with a moderate degree of confidence depending on serum estradiol, endometrial thickness and number of dominant follicles in the ovary. Other factors however need to be considered to increase the confidence of prediction, such as the type of insemination technique, sperm count of husband. A larger sample size and a survival analysis design is needed to assess the exact risk of having conception after each course of treatment