Severe Maternal Morbidity 3x Higher in Gestational Carriers

Gestational carriers face a significantly higher risk for severe maternal morbidity and other pregnancy complications than those conceiving naturally or via in vitro fertilization (IVF), according to a recent Canadian study.

These findings suggest that more work is needed to ensure careful selection of gestational carriers, reported lead author Maria P. Velez, MD, PhD, of McGill University, Montreal, Quebec, Canada, and colleagues.

“Although a gestational carrier should ideally be a healthy person, with a demonstrated low-risk obstetric history, it is not clear whether this occurs in practice,” the investigators wrote in Annals of Internal Medicine. “Moreover, the risk for maternal and neonatal adversity is largely unknown in this group.”

Study Compared Gestational Carriage With IVF and Unassisted Conception

To address these knowledge gaps, Velez and colleagues conducted a population-based cohort study in Ontario using linked administrative datasets. All singleton births at more than 20 weeks’ gestation with mothers aged 18-50 years were included from April 2012 to March 2021. Multifetal pregnancies were excluded, as were women with a history of infertility diagnosis without fertility treatment, and those who underwent intrauterine insemination or ovulation induction.

Outcomes were compared across three groups: Unassisted conception, IVF, and gestational carriage. The primary maternal outcome was severe maternal morbidity, defined by a validated composite of 41 unique indicators. The primary infant outcome was severe neonatal morbidity, comprising 19 unique indicators.

Secondary outcomes were hypertensive disorders, elective cesarean delivery, emergent cesarean delivery, preterm birth at less than 37 weeks, preterm birth at more than 32 weeks, and postpartum hemorrhage.

Logistic regression analysis adjusted for a range of covariates, including age, obesity, tobacco/drug dependence, chronic hypertension, and others. The final dataset included 846,124 births by unassisted conception (97.6%), 16,087 by IVF (1.8%), and 806 by gestational carriage (0.1%).

The weighted relative risk (wRR) for severe maternal morbidity was more than three times higher in gestational carriers than in those conceiving naturally (wRR, 3.30; 95% CI, 2.59-4.20) and 86% higher than in those conceiving via IVF (wRR, 1.86; 95% CI, 1.36-2.55). These stem from absolute risks of 2.3%, 4.3%, and 7.8% for unassisted, IVF, and surrogate pregnancies, respectively.

Moreover, surrogates were 75% more likely to have hypertensive disorders, 79% more likely to have preterm birth at less than 37 weeks, and almost three times as likely to have postpartum hemorrhage.

These same three secondary outcomes were also significantly more common when comparing surrogate with IVF pregnancies, albeit to a lesser degree. In contrast, surrogate pregnancies were associated with a 21% lower risk for elective cesarean delivery than IVF pregnancies (wRR, 0.79; 95% CI, 0.68-0.93).

Severe neonatal morbidity was not significantly different between the groups. These findings add to a mixed body of evidence surrounding both maternal and neonatal outcomes with gestational carriers, according to the investigators.

“Prior small studies [by Söderström-Anttila et al. and Swanson et al.] reported varying risks for preterm birth in singleton gestational carriage pregnancies, whereas a recent large US registry reported no increased risk for preterm birth compared with IVF, after accounting for multifetal pregnancy,” they wrote. “This study excluded multifetal pregnancies, a common occurrence after IVF, with reported higher risks for adverse outcomes. Accordingly, adverse maternal and newborn outcomes may have been underestimated herein.”

Causes of Worse Outcomes Remain Unclear

While the present findings suggest greater maternal morbidity among surrogates, potential causes of these adverse outcomes remain unclear.

The investigators suggested that implantation of a nonautologous embryo could be playing a role, as oocyte donation has been linked with an increased risk for hypertensive disorders of pregnancy.

“We don’t know exactly why that can happen,” Velez said in an interview. “Maybe that embryo can be associated with an immunological response that could be associated with higher morbidity during pregnancy. We need, however, other studies that can continue testing that hypothesis.”

In the meantime, more care is needed in surrogate selection, according to Velez.

“In our study, we found that there were patients, for example, who had more than three prior C-sections, which is one of the contraindications for gestational carriers, and patients who had more than five [prior] pregnancies, which is also another limitation in the guidelines for choosing these patients,” she said. “Definitely we need to be more vigilant when we accept these gestational carriers.”

But improving surrogate selection may be easier said than done.

The quantitative thresholds cited by Velez come from the American Society for Reproductive Medicine guidelines. Alternative guidance documents from the Canadian Fertility and Andrology Society and American College of Obstetricians and Gynecologists are less prescriptive; instead, they offer qualitative recommendations concerning obstetric history and risk assessment.

And then there is the regulatory specter looming over the entire field, evidenced by the many times that these publications cite ethical and legal considerations — far more than the average medical guidance document — when making clinical decisions related to surrogacy.

Present Study Offers Much-Needed Data in Understudied Field

According to Kate Swanson, MD, a perinatologist, clinical geneticist, and associate professor at the University of California San Francisco, the present study may help steer medical societies and healthcare providers away from these potential sand traps and toward conversations grounded in scientific data.

“I think one of the reasons that the Society for Maternal-Fetal Medicine and the maternal-fetal medicine community in general hasn’t been interested in this subject is that they see it as a social/ethical/legal issue rather than a medical one,” Swanson said in an interview. “One of the real benefits of this article is that it shows that this is a medical issue that the obstetric community needs to pay attention to.”

These new data could help guide decisions about risk and candidacy with both potential gestational carriers and intended parents, she said.

Still, it’s hard — if not impossible — to disentangle the medical and legal aspects of surrogacy, as shown when analyzing the present study.

In Canada, where it was conducted, intended parents are forbidden from paying surrogates for their services beyond out-of-pocket costs directly related to pregnancy. Meanwhile, surrogacy laws vary widely across the United States; some states (eg, Louisiana) allow only altruistic surrogacy like Canada, while other states (eg, California) permit commercial surrogacy with no legal limits on compensation.

Swanson and Velez offered starkly different views on this topic.

“I think there should be more regulations in terms of compensating [gestational carriers],” Velez said. “I don’t think being a gestational carrier should be like a job or a way of making a living.”

Swanson, who has published multiple studies on gestational carriage and experienced the process as an intended parent, said compensation beyond expenses is essential.

“I do think it’s incredibly reasonable to pay someone — a woman is taking on quite a lot of inconvenience and risk — in order to perform this service for another family,” she said. “I think it’s incredibly appropriate to compensate her for all of that.”

Reasons for compensation go beyond the ethical, Swanson added, and may explain some of the findings from the present study.

“A lot of these gestational carriers [in the present dataset] wouldn’t necessarily meet criteria through the American Society of Reproductive Medicine,” Swanson said, pointing out surrogates who had never had a pregnancy before or reported the use of tobacco or other drugs. “Really, it shows me that a lot of the people participating as gestational carriers were maybe not ideal candidates. I think one of the reasons that we might see that in this Canadian population is…that you can’t compensate someone, so I think their pool of people willing to be gestational carriers is a lot smaller, and they may be a little bit less selective sometimes.”

Velez acknowledged that the present study was limited by a shortage of potentially relevant information concerning the surrogacy selection process, including underlying reasons for becoming a gestational carrier. More work is needed to understand the health and outcomes of these women, she said, including topics ranging from immunologic mechanisms to mental health.

She also called for more discussions surrounding maternal safety, with participation from all stakeholders, including governments, surrogates, intended parents, and physicians too.

This study was funded by the Canadian Institutes of Health Research. The investigators disclosed no conflicts of interest. Swanson disclosed a relationship with Mitera.

Will Pass, DVM, is a veterinarian and freelance medical writer from Colorado.