IVF Associated With Higher Risk of Gestational Diabetes

BARCELONA — Mothers who undergo assisted reproduction are more likely to develop gestational diabetes than those who conceive naturally, shows a new meta-analysis presented here at the European Association for the Study of Diabetes (EASD) 2019 Annual Meeting.



Specifically, the analysis found that women who became pregnant through assisted reproductive techniques (ART) were 53% more likely to develop gestational diabetes than those who conceived naturally.

"This rigorous assessment of the best available evidence to date shows that singleton pregnancies achieved by in vitro fertilization (IVF) are linked with an increased risk of developing gestational diabetes compared with pregnancies conceived naturally," said Panagiotis Anagnostis, MD, clinician and researcher from the Aristotle University of Thessaloniki, Greece, who presented the results in a poster and during a press conference at the meeting.

He stressed that the findings highlight the importance of early detection of gestational diabetes in women who fall pregnant after ART, which as well as IVF, covers those conceiving through intracytoplasmic sperm injection (ICSI).

"This can lead to timely and effective interventions, especially for women with pre-existing risk factors for gestational diabetes including polycystic ovary syndrome (PCOS), obesity, increased maternal age, and family history of type 2 diabetes," Anagnostis said.

"These women should receive intensified lifestyle interventions during the IVF period and first trimester of pregnancy because it will reduce risks of developing gestational diabetes," he noted.

Adrian Heald, MD, from the University of Manchester, UK, commented: "This is very sobering for those of us involved in assisted conception work."

He continued: "Do you have any sense of the long-term consequences...because we know from UK data that if we look at a 10- to 15-year time scale with gestational diabetes, around 30% of women develop full-blown type 2 diabetes."

Is the ART group "a different group, do you think?" Heald wondered.

Anagnostis replied that it's not known at present. "Long-term prospective data on these women, looking at 10 to 20 years after pregnancy, are needed to elucidate this issue."

Large Study Allows for Precise Risk Estimates
Estimates suggest more than half a million babies are born from IVF and ICSI each year. Pregnancies from ART are known to result in an increased risk of obstetric and perinatal complications, but any potential association with gestational diabetes has remained unclear, with prior studies showing contradictory results, explained Anagnostis.

To resolve this uncertainty, the endocrinologist and his colleagues conducted a systematic review to determine whether singleton pregnancies after ART (IVF or ICSI) were associated with a higher risk of gestational diabetes compared with normal pregnancies.

They included studies published between 1995 and July 2019, but any involving women with PCOS or multipregnancy history were excluded because these conditions are already known to be associated with increased gestational diabetes risk.

A total of 38 cross-sectional studies (17 with matched with controls and 21 unmatched) were included, of which 13 were prospective and 25 were retrospective.

Together, the studies involved nearly 2 million women, of which over 163,000 were diagnosed with gestational diabetes.

A diagnosis of gestational diabetes was made in 4776 of 63,760 women who became pregnant through ART and in 158,526 of 1,870,734 women who conceived spontaneously.

"This number of women allows for precise risk estimates of this association," remarked Anagnostis.

"We found that women who have undergone ART were at increased risk of gestational diabetes, with a relative risk of 1.53 [CI 95%, 1.39 - 1.69]."

"When subgroup analyses were done of matched and unmatched studies we found similar results," he reported.

Specifically, further analysis of the 17 studies in which women were matched for age, height, weight, smoking status, and ethnic origin indicated that women who underwent ART were over 40% more likely to develop gestational diabetes compared with spontaneous conception, with a relative risk of 1.42 (CI 95%, 1.17 - 1.72).

The corresponding figure for the unmatched studies was 1.58 (CI 95%, 1.40 - 1.78).

Exact Mechanism for Association Unclear
The endocrinologist said that the exact mechanism for the association remains unclear, however.

"Whether the association observed between ART and gestational diabetes is explained by the presence of infertility per se or the ART procedure performed, cannot be evaluated currently," he stressed.

But he suggested that "the use of progesterone during the luteal phase and the first trimester may be associated with increased risk of gestational diabetes since progesterone is known to increase insulin resistance."

"Also, vitamin D deficiency may provide a common underlying pathway since it has been both associated with infertility and gestational diabetes," he added.

Anagnostis and Heald have reported no relevant financial relationships.

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