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Too Much of a Good Thing: Multiple Gestations With Intrauterine Insemination.

The majority of patients with infertility would prefer to conceive with minimal medical intervention. This is often dually motivated— to allow pregnancy to occur in the most natural setting, but also to minimize cost. As a result, most patients start, and many complete, their fertility journey with ovarian stimulation in conjunction with timed intercourse or an intrauterine insemination. The goal of fertility treatment is a healthy baby. A singleton pregnancy provides the best path toward that goal given the increased maternal and fetal morbidity of multiple gestations.1 Fertility treatment is a known major contributor to twin and higher-order multiple gestation pregnancy.2 Although infertility patients often fear that in vitro fertilization (IVF) puts them at greatest risk for a multiple gestation pregnancy, this fear is increasingly misplaced. Advances in assisted reproductive technology and increased patient and health care provider acceptance of single embryo transfers have changed IVF care, reducing the number of embryos transferred and multiple gestations.3 The majority of multiple gestation pregnancies resulting from fertility treatment are a result of non-IVF treatment.4 In this issue of Obstetrics & Gynecology, Evans et al5 (see page 1005) present the results from their large retrospective cohort study (50,473 intrauterine insemination cycles) examining the risk of multiple gestation after ovarian stimulation based on mature follicle number. Their cohort included patients treated at a single, large fertility practice over a 14-year period; the majority of patients had unexplained infertility (39.9%), polycystic ovarian syndrome (PCOS) (20.1%), or mild male factor infertility (9.2%). Ovarian stimulation was performed with clomiphene alone (28.4%), clomiphene with gonadotropins (39.9%), or gonadotropins alone (22.9%). Fewer than 10% of cycles were performed with letrozole. The authors report pregnancy rates ranging from 4.1% to 21.8% per cycle. Overall, the chance of pregnancy increased with each additional mature follicle; however, the risk of multiple pregnancy increased more. When analyzed by age group, in women younger than age 38 years, there was a significant jump in pregnancy rate (adjusted odds ratio 1.3) when comparing two mature follicles with a single follicle but only a slight additional increase when three, four, or five mature follicles were present. In contrast, chance of a multiple pregnancy increased considerably with each increase in follicle number (adjusted odds ratios 3.6–9.9), and more than a quarter of pregnancies were multiple gestations if patients had more than three mature follicles. In women aged 38–40 years, these findings were similar but attenuated. In women older than age 40 years, the increase in follicle number increased pregnancy rates without an increase in multiple gestations until the mature follicle count reached five. Based on this, the authors suggest that caution should be used if proceeding with See related article on page 1005.