Ovarian stimulation increases the risk of ectopic pregnancy for fresh embryo transfers: an analysis of 68,851 clinical pregnancies from the Japanese Assisted Reproductive Technology registry

Ovarian stimulation protocols were significantly associated with an increased risk of ectopic pregnancy. In particular, ovarian stimulation using clomiphene had the highest risk of ectopic pregnancy compared with other stimulation protocols.

Like Comment
Related Content

VOLUME 114, ISSUE 6, P1198-1206


Seung Chik Jwa, M.D., Ph.D., M.P.H., Sachie Seto, M.D., Ph.D., Masashi Takamura, M.D., Ph.D., Akira Kuwahara, M.D., Ph.D., Takeshi Kajihara, M.D., Ph.D., Osamu Ishihara, M.D., Ph.D.



To evaluate the risk of ectopic pregnancies (EPs) for fresh cycles according to different ovarian stimulation protocols.


Registry-based retrospective cohort study.


Not applicable.


A total of 68,851 clinical pregnancies after fresh single embryo transfer between 2007 and 2015.

Intervention (s)


Main Outcome Measure(S)

Ectopic pregnancies. Odds ratios and 95% confidence intervals for EPs were calculated by using generalized estimating equations adjusted for potential maternal and treatment characteristics.


Among 68,851 clinical pregnancies, 1,049 (1.46%) cases of EP were reported. Compared with natural cycles, all ovarian stimulation protocols were associated with a significantly increased risk of EP. Ovarian stimulation with clomiphene (CC) demonstrated the highest odds ratios for EPs. Significant associations between ovarian stimulation protocols and EP compared with natural cycles were prominent when the number of retrieved oocytes was low (1–3) to moderate (4–7), but there were no significant associations when the number of retrieved oocytes was high (≥8).


Ovarian stimulation protocols were significantly associated with an increased risk of EP. In particular, ovarian stimulation with CC had the highest risk of EP compared with other stimulation protocols. Further studies are essential to investigate possible confounding factors for different ovarian stimulation protocols, especially CC, and the risk of EP.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.