Optimal follicular size to trigger ovulation in IUI cycle tied to endometrial thickness: Study
When performing ovulation induction (OI) cycles combined with intrauterine insemination (IUI), the use of exogenous human chorionic gonadotropin (hCG) to trigger ovulation remains a popular practice. This treatment is especially valuable for women who cannot reliably detect the spontaneous luteinizing hormone (LH) surge. The timing of hCG administration is not well standardized but usually relies on there being at least one follicle greater than 18 mm in mean diameter at ultrasound imaging. This timing is important because premature administration of hCG acts like a premature LH surge and may result in follicular atresia. Delayed hCG administration can happen after ovulation has already occurred, thus negating any potential benefit.
Studies comparing the leading follicle diameter in natural cycles with CC cycles found that CC cycles have significantly larger leading follicles, measuring between 18 and 30 mm. Because of this wide range, many investigators did not consider this parameter to be a prognostic indicator for IUI success.
During the last decade, the use of aromatase inhibitors for ovulation induction has rapidly expanded. Studies have shown the efficacy of aromatase inhibitors in ovulation induction in patients who have a poor response to CC, in patients with polycystic ovary syndrome who are resistant to CC, and in patients with unexplained infertility.
Authors Palatnik et al investigated the optimal size of the leading follicle before hCG administration in cycles with CC and letrozole. Secondarily, examined whether there is a difference in the optimal leading follicle size between cycles with CC and letrozole.
This retrospective analysis included women undergoing ovulation induction followed by IUI at an academic reproductive medicine center from 2004 to 2009. The study group included all women undergoing a first cycle of IUI in our center after treatment with either CC or letrozole in which a midcycle ultrasound was performed and ovulation was triggered with hCG.
The women in their first ovulation induction/IUI cycle underwent transvaginal ultrasound monitoring between cycle days 11 and 13 after receiving 5 days of treatment with 100 mg of CC daily or 5 mg of letrozole daily starting on days 3 to 5. At the time of the ultrasound, the mean diameter of the follicle was calculated from measurements in two perpendicular planes for any follicles measuring greater than 14 mm. If at least one follicle ≥18 mm in mean diameter was detected, hCG was administered the same morning, and IUI was scheduled 24 hours later.
Patients were instructed to obtain a quantitative serum hCG measurement 14 days after the insemination if they did not menstruate. If the result was positive, the patient was scheduled for a transvaginal ultrasound 6 to 7 weeks after the last menstrual period to document the pregnancy location and fetal heart activity. Main Outcome included Leading follicle diameter and intrauterine insemination outcome.
Eight percent of patients were excluded because their leading follicle was less than 18 mm by days 11 to 13. Pregnancy was recorded as clinical pregnancy with fetal heart activity seen at 6- to 7-week transvaginal ultrasound.
For both CC and letrozole, higher pregnancy rates were achieved when the leading follicles were in the 23 to 28 mm range. The optimal size of the leading follicle was not statistically significantly different between cycles using CC or letrozole. However, for each endometrial thickness, the optimal follicular size of the leading follicle was different.
Each additional millimeter of endometrial thickness increased the optimal follicular size by 0.5 mm. Thicker endometrial lining led to a higher probability of pregnancy.
In this study, authors examined the optimal follicular size before hCG administration to yield the highest pregnancy rates in IUI cycles stimulated using CC or letrozole.
In this study, the important factors for clinical pregnancy after IUI were found to be maternal age, primary infertility diagnosis, endometrial thickness, the size of the leading follicle, and the drug type. Sperm motility and the presence of other mature follicles were not found to be statistically significantly correlated with pregnancy. One possible explanation for the sperm motility not being a predictive factor of the cycle outcome may be because the majority of men in our couples had total motile sperm count values above the threshold.
In this study, authorz found that there is an optimal size for the leading follicle that maximizes the probability of pregnancy, with lower rates for both smaller and larger leading follicles. This optimal size is influenced by the endometrial thickness. For both drugs, higher pregnancy rates were achieved with the leading follicle being in the range of 23 to 28 mm. Within that range, pregnancy rates were higher when the larger follicles were accompanied by a thicker endometrium and vice versa. These findings can be seen as a similar response of the endometrium and the follicles to the ovulation-induction agent, letrozole or CC: an appropriate response affected both the follicles and the endometrium in the same way. Possibly, this reflects coordination between follicular growth and the endometrial lining.
Larger follicles would be expected to produce higher levels of estradiol that would then stimulate the endometrial lining more, and smaller follicles would produce lower levels of estradiol and thus produce a thinner lining. When this coordination is disrupted, lower pregnancy levels are the result. The size of the leading follicle that resulted in a pregnancy was not statistically significantly different in cycles with CC and letrozole. However, it appears that cycles stimulated with CC had a wider range of follicle sizes, which resulted in similar rates of pregnancy as compared with letrozole.
Endometrial lining was found to be a predictive factor of achieving pregnancy, and thicker endometrial lining resulted in higher pregnancy rates when the leading follicle size was close to the optimum (P=.002).
The authors concluded, "Our study has shown that the optimal size of the leading follicle in ovulation induction with CC and letrozole is similar for both drugs and is closely related to the endometrial thickness of the cycle. Keeping that relationship in mind can help in planning the IUI cycle and in timing the hCG administration."
Source: Anna Palatnik, Estil Strawn, Aniko Szabo and Paul Robb, Fertility and Sterility