Short answer: It depends on the medicine and the treatment. The Clomid label reports multiples in 7.98% of pregnancies, mostly twins. Injectable gonadotropins run higher: in Gonal-f trials, multiples were 20% of live births with ovulation induction and 35.1% with IVF and other assisted reproduction. In a large trial in PCOS, twins were 3.4% with letrozole and 7.4% with clomiphene.
| Medicine | Setting | Rate in the label |
|---|---|---|
| Clomid (clomiphene) | Ovulation induction, label trials | 7.98% of pregnancies: 6.9% twins, 0.5% triplets, 0.3% quadruplets, 0.1% quintuplets |
| Gonal-f RFF (follitropin alfa) | Ovulation induction | 20% of live births (section 5.6) |
| Gonal-f RFF | Assisted reproduction (ART) | 35.1% of live births (section 5.6) |
| Menopur (menotropins) | IVF trial | 35.3% of 85 pregnancies on ultrasound (section 5.5) |
| Ovidrel (hCG trigger) | ART studies | 17 of 55 live deliveries (30.9%) |
| Ovidrel | Ovulation induction trial | 2 of 15 live deliveries (13.3%) |
| Follistim AQ (follitropin beta) | All uses | No rate given; multiples reported with all gonadotropins (section 5.5) |
These figures come from different study designs, so they are not a head-to-head ranking. The Ovidrel label notes that in ART the risk of multiples tracks the number of embryos transferred.
Letrozole (Femara) is approved for breast cancer in postmenopausal women; its use for ovulation is off-label. In a trial of 750 women with polycystic ovary syndrome (Legro 2014), twin pregnancy was 3.4% with letrozole and 7.4% with clomiphene; the difference was not statistically significant. Live births were higher with letrozole (27.5% vs 19.1%). More on that trial is in letrozole vs Clomid.
Fertility medicines can cause more than one egg to mature in a cycle. The Gonal-f and Menopur Patient Information say a pregnancy with more than one baby raises the health risk for the mother and the babies. The Clomid label reports that 83.26% of infants from multiple births survived, against 98.16% from single births in its pregnancy outcome table.
The labels describe monitoring as the main tool: ultrasound of growing follicles, with blood estradiol, tracks follicle growth and the timing of the trigger shot, and helps limit both multiples and ovarian hyperstimulation syndrome. Every gonadotropin label says the woman and her partner should be told about the chance of multiples before treatment starts.
Clinics can describe their own rates for a given medicine, dose and plan, which may differ from label trials. Questions worth asking include how many follicles would lead to a cancelled cycle and, for IVF, how many embryos will be transferred. Dose Track can log each injection by cycle day, with the dose in IU and the vial or pen used, so the record lines up with monitoring visits.
Read more on Dose Track: Letrozole vs Clomid · Gonal-f side effects · Ovulation induction · Ovarian hyperstimulation syndrome