Optimal follicular size for ovulatory trigger in natural and clomiphene citrate intrauterine insemination cycles

Abstract

Intrauterine insemination (IUI) during a natural cycle (NC) or following ovulation induction with clomiphene citrate (CC) forms the mainstay of fertility treatment in many young patients. IUIs in such patients are frequently performed after administration of a human chorionic gonadotropin (hCG) ovulatory trigger. The primary objective of this study is to identify the optimal lead follicular size for an ovulatory trigger in either NC or CC IUI cycles. Retrospective cohort study. Patients <40 years of age, with patent fallopian tubes, a normal uterine cavity, and a male partner with >15 million sperm/mL, undergoing an IUI in either a NC or CC ovulation induction cycle between 2004 and 2013 were analyzed for inclusion. All patients with a spontaneous LH surge or undergoing successive IUIs in the same treatment cycle were excluded. The hCG ovulatory trigger was administered either subcutaneously or intramuscularly, after visualization of a >17 mm follicle in the NC group or >19 mm follicle in the CC group, and an endometrial thickness of >7 mm in both groups. IUIs were performed 24-30 hours following the ovulatory trigger. Clinical pregnancy rates were plotted for the NC and CC groups against lead follicular size, in increments of 1 mm beginning at 17 mm. Odds ratios (OR) for clinical pregnancy at different lead follicular sizes were calculated by using 17 mm and 19 mm as reference values for the NC and CC groups, respectively. 3272 IUI cycles met inclusion criteria: 1201 NC and 2071 CC. The median age in the NC and CC groups was 36.4 (31.4-41.4) years and 34.3 (29.8-38.8) years, respectively. In the NC group, the clinical pregnancy rate (14%) was highest when the ovulatory trigger was administered at a lead follicular size of 19 mm compared to the reference group of 17 mm (8%). However, these odds were not statistically significant (OR 1.80, 95% CI 0.73-4.41). The aforementioned odds remained unchanged even after adjusting for age. In contrast, the clinical pregnancy rate in the CC group was highest when the lead follicular size was 22 mm at the time of the ovulatory trigger (16%). Compared to the reference group of 19 mm, the odds for clinical pregnancy with a lead follicle of 22 mm was 2.14 times higher (OR 2.14, 95% CI 1.20-3.83; P=0.01). The higher odds for clinical pregnancy persisted even after stratifying for age: 25-35 years (OR 2.55, 95% CI 1.25-5.20) and 35-40 years (OR 1.90, 95% CI 1.01-3.58). Our results suggest that administration of a hCG ovulatory trigger at a lead follicular size of 22 mm is associated with higher odds of clinical pregnancy in patients undergoing IUI following ovulation induction with CC. Although triggering at a lead follicular size of 19 mm in the NC group is also associated with an increased odds of clinical pregnancy, these odds remain non-significant when compared to the reference group of 17 mm.