IVF Ups Risk of Severe Pregnancy Complications

Becky McCall

February 07, 2019

Women who undergo in vitro fertilization (IVF) are more likely to experience severe complications of pregnancy, including severe postpartum hemorrhage, admission to the intensive care unit, and sepsis, compared with women who conceived without assisted reproduction techniques.

Published in the February 4 issue of CMAJ, the research examined the association between infertility treatment and severe maternal morbidity in pregnancy and the postpartum period.

The study also found that noninvasive infertility treatment — for example, intrauterine insemination — does not place women at increased risk of complications, as opposed to "invasive" therapies, such as IVF.

"We found that the women who received infertility treatment, especially in vitro fertilization, were about 40% more likely to experience a severe pregnancy complication compared with women who gave birth without any treatment," said lead author Natalie Dayan, MD, from the Research Institute at McGill University Health Centre, Montreal, Quebec, Canada, in a press release from her institution.

Dayan stressed, however, that "it is important to remember that the absolute number of women who develop these complications remains quite small, meaning that for most women who cannot conceive naturally, this treatment is a very safe and effective method of becoming pregnant and having a child."

She and her coauthors point out that it remains to be determined what, if any, specific components of IVF might affect outcomes. It will also be important to figure out if the increased risk is any reflection on those who require or choose IVF. Understanding patient- and treatment-specific predictors of severe maternal morbidity might influence the type of treatment a woman is offered, they add.

Maternal Factors Associated With Some of the Increase in Morbidity

Using population-based registries from Ontario between 2006 and 2012, pregnancies conceived using infertility treatment were compared with those achieved without assistance.

Infertility treatment included ovulation induction and/or intrauterine insemination (noninvasive treatment) or IVF (with or without intracytoplasmic sperm injection; invasive treatment).

Comparisons used propensity score matching based on demographic, reproductive, and obstetric factors.

Data on 813,719 live and stillbirths were analyzed, and 11,546 women who conceived using infertility treatment were identified and matched with 47,553 women who conceived without assistance.

Those with assisted conception were typically older, reported higher incomes, and were more often first-time mothers and carried multiple fetuses.

The primary outcome was a validated composite of severe maternal morbidity (near-fatal event) or maternal death from 20 weeks' gestation to 42 days postpartum.

In Canada, severe maternal morbidity (15 per 1000 hospital deliveries) is more common than maternal death (10 per 100,000 hospital deliveries).

The analysis showed that a severe maternal morbidity event or death occurred in 356 pregnancies resulting from infertility treatment (30.8 per 1000) and in 1054 conventional pregnancies (22.2 per 1000), generating an adjusted relative risk (RR) of 1.39.

"After propensity score matching, the relative risk of severe maternal morbidity or death was attenuated from 2.17 to 1.39, suggesting that some of the association between infertility treatment and severe maternal morbidity is explained by maternal factors rather than by the treatment," the researchers explain.

Over the last number of years, there have been increased efforts to promote optimal maternal health before infertility treatment, and fertility specialists now often choose to implant only one embryo per mother, to avoid risks associated with multiple pregnancies, they note.

But the study does suggest a small added risk from the treatment itself.

Highest Risk of Maternal Morbidity With Invasive Infertility Techniques

When the different types of infertility treatment were compared, severe maternal morbidity or death occurred more often in those receiving invasive than noninvasive infertility treatment, in 235 pregnancies (39.3 per 1000) versus 121 pregnancies (21.7 per 1000), respectively.

Noninvasive and invasive infertility treatments generated adjusted RRs of 0.98 and 1.77 for severe maternal morbidity or death respectively, compared with pregnancies conceived without assistance.

"The significant difference in the effect of IVF compared with noninvasive treatment suggests that factors associated with IVF may contribute to severe maternal morbidity," the researchers say

The higher risk of severe maternal morbidity was most notable for certain specific events — severe postpartum hemorrhage, intensive care unit admission, and sepsis — although hysterectomy and cardiac conditions were also more likely to occur among those who received infertility treatment.

As pregnancy complications are often sudden and difficult to predict, it is important to identify women who may be at risk for these "near miss" events, she and her colleagues conclude.

The authors have reported no relevant financial relationships.

CMAJ. 2019;191:E118-E127. Full text

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