How Does Use of ART Affect Maternal Morbidity?

Peter Kovacs, MD, PhD


May 11, 2016

Severe Maternal Morbidity and the Use of Assisted Reproductive Technology in Massachusetts

Belanoff C, Declerq ER, Diop H, et al
Obstet Gynecol. 2016;127:527-534


Complications and adverse outcomes are very difficult to accept during a pregnancy or delivery, as they typically happen to a young and otherwise healthy woman and often affect the baby as well as the mother. It is estimated that there are 1 million fetal losses per year in the United States, with the majority occurring before week 20 of gestation.[1]

A pregnancy has a significant impact on the mother. Perinatal outcome cannot be considered optimal when a healthy newborn is delivered but the mother has an adverse outcome. Pregnancy-related maternal death has been increasing since the 1980s.[2] Therefore, it is important to study the association between certain maternal characteristics, pre- and periconceptional events, and prenatal interventions and pregnancy outcome. This retrospective study evaluated the impact of assisted reproductive technology (ART) on severe maternal morbidity.

The Study

The authors evaluated the impact of fertility status (fertile; subfertile, no ART; subfertile, with ART) on severe morbidity during pregnancy. Morbidity was considered severe when it was life-threatening (acute cardiovascular event, thromboembolism, coagulation defects, renal failure, sepsis, shock, anesthesia complications, respiratory distress, need for hysterectomy, need for intubation, need for blood transfusion). Data were collected from the Society for Assisted Reproductive Technology database as well as from birth certificates, fetal death records, and hospital utilization data from the Massachusetts-based Pregnancy to Early Life Longitudinal Data System.

Researchers evaluated 458,918 deliveries with complete data from 2004-2010. Singleton and twin pregnancies, as well as vaginal and C-section deliveries, were analyzed separately. There were 436,487 deliveries in fertile women, 13,677 deliveries in subfertile women using ART, and 8754 deliveries in subfertile women not using ART. Overall, 1.16% of deliveries were affected by severe maternal morbidity (1.09% in fertile women, 1.44% in subfertile women not using ART, and 3.14% in subfertile women using ART).

When singleton, vaginal deliveries were considered, those undergoing ART were more than twice as likely to be affected by severe morbidity when compared with fertile women (OR, 2.27; 95% CI, 1.78-2.88) and almost twice as likely as subfertile women not using ART (OR, 1.97; 95% CI, 1.3-3). In the case of twin vaginal deliveries, the risk was not increased among subfertile women undergoing ART. Subfertile women who had no ART treatment were not at increased risk for severe maternal morbidity when compared with fertile women.

When singleton C-section deliveries were analyzed, subfertile women who underwent ART were at increased risk for severe morbidity when compared with fertile women (OR, 1.67; 95% CI, 1.4-1.98). The risk was increased when subfertile women undergoing ART were compared with subfertile women who didn't use ART (OR, 1.75; 95% CI, 1.3-2.35). In the case of twin C-section deliveries, subfertile women undergoing ART were at increased risk for severe perinatal morbidity when compared with fertile women (OR, 1.48; 95% CI, 1.14-1.93). The risk among subfertile women not using ART to conceive did not differ from the risk observed in fertile women.


Since the birth of the first baby conceived by in vitro fertilization (IVF), ART has been used increasingly.[3,4] It is estimated that more than 5 million children conceived in vitro have been born worldwide, and in the developed world up to 5% of children are born following successful IVF treatments. It is well known that the pregnancy outcome following IVF is not as good as in spontaneous conceptions, but the extra risk was believed to be due to the higher rate of multiples.

It is also known that infertile women differ from fertile women. They are more likely to be older and more likely to be affected by medical problems that lower their overall chance to conceive (higher BMI, more diabetes, hypertension, endometriosis, polycystic ovary syndrome, anatomic defects such as fibroids, etc.). These problems affect not only their chance to conceive but also the outcome of the pregnancy. These risk factors, however, are likely to be present among subfertile women, too, who may ultimately conceive on their own. Therefore, when pregnancy outcome is assessed, fertile women need to be compared with subfertile women conceiving on their own or via ART. This way, the impact of ART treatment (medication use, embryo culture) itself can be evaluated.

On the basis of this study's results, subfertile women undergoing ART are the most likely to be affected by severe morbidity. Other studies have drawn similar conclusions, although there is no consensus about whether it is infertility itself or the technology that carries the additional risks.[5]

When a subfertile couple is counseled, they need to be informed about the perinatal maternal and neonatal risks. Underlying medical conditions must be looked for and addressed before treatment is initiated. The risk that a pregnancy carries should not be further augmented by a multiple pregnancy; every effort should be made to achieve a singleton pregnancy. Obstetricians also need to be aware of the extra risk that subfertility in itself carries and adjust the prenatal care accordingly.



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