Hassan Sallam^1,2 Ola Mustafa Saleh¹, Abdel-Fattah Agameya¹ and Nooman Sallam²
Departments of Obstetrics and Gynaecology¹, University of Alexandria and the Alexandria Fertility and Assisted Reproduction Center², Alexandria, Egypt

Objective: To study the effect of serum LH and plasma progesterone rise on the day of HCG administration on the clinical outcome of anovulatory patients treated with gonadotropins.

Design: A prospective cohort study.

Materials and methods: Sixty consecutive anovulatory patients attending our infertility clinic and treated for ovarian stimulation with gonadotropins were studied during their first cycle of treatment. All patients had normogonadotrophic hypogonadism (WHO group II) and had failed to become pregnant on clomiphene citrate therapy (up to 150 mg/day for 5 days). All patients were aged 20 to 38 years with a mean (±SD) of 26.7 (±9.2) years. All male partners had normal semen parameters according to the WHO standards. Patients with hyperprolactinaemia and those with congenital adrenal hyperplasia were excluded, as well as those with other causes of infertility. The mean (±SD) basal (day 3) serum FSH and LH levels were 7.27 (±1.82) mIU/mL and 7.57 (±0.78) mIU/mL, respectively. The mean (±SD) basal (day 3) LH/FSH ratio was 1.09 (±014) mIU/mL. Human menopausal gonadotropins (150 IU) were administered by daily IM injections starting day 5 of the menstrual cycle. Monitoring was effected by transvaginal ultrasound scanning of the follicles and the dose of gonadotropins adjusted accordingly. HCG (5000 IU) was administered by IM injection when 2 follicles reached 18 mm in diameter and venous blood was withdrawn on the same day and the serum/plasma kept at -20°C until the time of the LH and progesterone assay. Eighteen patients became pregnant, of whom 17 reached clinical viability (beating heart on ultrasound) and one had a miscarriage. Power calculation regarding the premature rise or otherwise of serum LH revealed that a minimum of 17 treatment cycles was needed to study in each group to achieve an 80% study power at the 5% level significance level.

Results: The mean (±SD) of serum LH and plasma progesterone levels on the day of HCG administration were 11.10 (±9.08) mIU/mL and 2.68 (±0.14) ng/mL, respectively. Twenty nine patients (48.3%) had an LH rise of >10 mIU/mL. Of those 8 became pregnant (27.6%) compared to 10 pregnancies (32.3%) in the 31 patients with no LH rise (P =0.693). Twelve patients (20%) had a rise of plasma progesterone (=>1.5 ng/mL) and 8 patients (13.3%) had a rise of =>3 ng/mL and none of these patients became pregnant, compared to 18 pregnancies in the 48 patients (37.5%) with plasma progesterone <1.5 ng/mL (P < 0.02). The serum LH and plasma progesterone levels were 10.8 mIU/mL and 0.9 ng/mL, respectively in the patient who miscarried.

Conclusions: Contrary to accepted convention, the premature rise of serum LH on the day of HCG administration does not seem to affect the clinical outcome in anovulatory patients treated with gonadotropins. However, the rise of progesterone >1.5 ng/mL is detrimental to the clinical outcome in those patients. Converting the cycle to IVF in those patients and freezing all the embryos for transfer in subsequent cycle(s) is suggested.