New Personalized Tool Predicts Pregnancy After Ovulation Induction or Controlled Ovarian Stimulation
Key findings
- The goal of this study was to develop a prediction tool suitable for individual women to calculate their chance of pregnancy after ovulation induction or controlled ovarian stimulation
- Predictive factors were determined in a combined secondary analysis of two multicenter randomized trials of various fertility drugs; one involved 750 women with polycystic ovary syndrome and the other involved 900 women with unexplained infertility
- The resulting formulas had fair power for predicting pregnancy (area under the curve (AUC) 0.78 for cycle 1 and 0.70 for cycle 4) and good to excellent power for predicting multiple pregnancy (AUC 0.78 for cycle 1 and 0.86 for cycle 4)
- An easy-to-use prediction tool is now available online for use by women with polycystic ovary syndrome or unexplained infertility
Since 2015, the Society of Assisted Reproductive Technology has offered an online tool where patients undergoing in vitro fertilization (IVF) can calculate their probability of pregnancy after one or two treatment cycles.
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Now a similar calculator is available for patients undergoing ovulation induction or controlled ovarian stimulation (OI/OS). Irene C. Souter, MD, fertility specialist in the Fertility Center and Reproductive Endocrinology Unit at Massachusetts General Hospital, and colleagues in the Reproductive Medicine Network of the National Institute of Health and Human Development describe its development in Fertility and Sterility.
Methods
The researchers conducted a secondary analysis of two multicenter, randomized, controlled trials completed by the Reproductive Medicine Network:
- Pregnancy in Polycystic Ovary Syndrome (PCOS) II (PPCOSII)—750 women with PCOS (defined here as anovulation with either hyperandrogenism or polycystic ovaries) were randomized to up to five cycles of OI/timed intercourse using either clomiphene or letrozole
- Assessing Multiple Intrauterine Gestations after Ovulation Stimulation (AMIGOS)—900 women with unexplained infertility were randomized to clomiphene, letrozole or gonadotropins for up to four cycles of OS/intrauterine insemination
All 1,650 women were ages 18 to 40 years and had a normal uterine cavity and at least one patent fallopian tube. Women in AMIGOS also showed evidence of regular ovulation and normal ovarian reserve.
Clinical Pregnancy
The variables that predicted clinical pregnancy were:
- Patient's age
- Patient's body mass index
- Partner's age
- Type of treatment (clomiphene, letrozole or gonadotropins)
- Maximum medication dose
Notably, none of these predictors was statistically significant in treatment cycle 5.
Multiple Pregnancy
The variables that predicted multiple pregnancy were the same as above (except age) plus:
- Baseline antimüllerian hormone level
- Baseline antral follicle count
- Prior parity
- Type of infertility diagnosis
- Peak estradiol level
- Total number of preovulatory follicles
The most consistent of these factors were treatment with gonadotropins. 56% of multiple pregnancies were conceived in gonadotropin-stimulated cycles.
The New Calculator
A model that incorporated these variables had predictive power as follows:
- Clinical pregnancy—Fair (area under the receiver operating characteristic curve [AUC], 0.78 for cycle 1 and 0.70 for cycle 4)
- Multiple pregnancy—Good to excellent (AUC, 0.78 for cycle 1 and 0.86 for cycle 4)
Application of the Calculator
The calculator is now available online but should be used only by women with a diagnosis of PCOS or unexplained infertility who meet the other inclusion criteria for PPCOSII or AMIGOS. The model has yet to be validated in women with other diagnoses.
Another limitation of the calculator is that it can't predict the outcomes of the fifth cycle, but fifth cycles are rarely pursued by patients given ART availability. As more data become available, it may be expanded.
Importantly, predictions can be made before medication is started. This may help women and their clinicians choose the medication, estimate the cumulative probability of clinical pregnancy and decide whether IVF is likely to be a better option.
The online tool also aids in weighing the chance of clinical pregnancy against the risk of a multiple pregnancy for each individual cycle, in real time. This will guide shared decision-making about aborting a particular cycle if the risks seem to outweigh the benefits.
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