Pregnancies in women aged 45 years or older are becoming increasingly common in Italy, often through assisted reproductive technology (ART).

A multicentre cohort study showed that assisted conception in this age group is linked with significantly higher maternal morbidity, especially when donor oocytes are used, while neonatal outcomes remain largely comparable with spontaneous conception (SC). 

The findings underscore a growing clinical challenge as more women of advanced reproductive age pursue pregnancy through assisted methods, highlighting the need for comprehensive preconception counselling and specialized obstetric care.

In Italy, the mean age at first birth is 32.4 years, yet a substantial number of women now give birth at 45 or older. Many pregnancies at very advanced maternal age (45-49 years) and extremely advanced maternal age (≥ 50 years) rely on ART. 

Because maternal age and ART both increase the risk for perinatal morbidity, an Italian research group conducted a cohort study examining maternal and neonatal outcomes in pregnancies among women older than 45 years, with a focus on mode of conception (SC vs ART) and, within ART, the origin of the oocytes.

The findings published in Acta Obstetricia et Gynecologica Scandinavica showed higher maternal morbidity in pregnancies achieved with ART, particularly when donor oocytes were used. Neonatal outcomes did not differ significantly across conception types.

Study population

The study included women ≥ 45 years of age with singleton pregnancies delivered at 22 weeks gestation or later between 2016 and 2022 across five Italian academic hospitals. Pregnancies were categorized as SC or ART, and ART pregnancies were further stratified by oocyte origin into homologous ART (ART HO) and heterologous ART (ART HE).

Multivariable logistic regression was used to evaluate the associations between conception type and obstetric outcomes after adjustment for key confounders.

Among the 557 pregnancies, 495 (88.9%) involved women aged 45-49 years, and 62 (11.1%) involved women ≥ 50 years of age. ART accounted for 63.9% of all pregnancies. Nulliparity was more frequent in ART vs SC (86.5% vs 34.8%; P < .001).

Compared with SC, ART was associated with fourfold higher adjusted odds of caesarean delivery (aOR, 4.20; 95% CI, 2.99-4.92; P < .001) and increased postpartum hemorrhage (aOR, 2.72; 95% CI, 1.75-4.23; P < .001). Neonatal outcomes did not differ significantly.

Within ART, ART HE was associated with increased odds of gestational diabetes (aOR, 1.97; 95% CI, 1.10-3.55; P = .024) and manual placental removal (aOR, 10.45; 95% CI, 1.23- 88.46; P = .031) compared with ART HO. 

The wide CI reflects the low event rate in both groups and limits precision, warranting cautious interpretation.

The only significant neonatal difference was a higher rate of 1-minute Apgar scores < 7 in ART HO (13.3% vs 5.1%; P = .007). No significant differences were found for 5-minute Apgar score < 7, NICU admission, respiratory support, or stillbirths.

Clinical Implications

According to the researchers, the higher rate of caesarean delivery in ART vs SC, including planned procedures (50.6% vs 25.9%), likely reflects both increased obstetric complications and clinical caution in managing precious pregnancies. They further suggest that differences in embryo handling, freezing methods, and stimulation protocols may contribute to observed variability across ART approaches.

“Given the growing reliance on ART among older women, especially the increasing use of donor oocytes, our findings emphasize the need for comprehensive preconception counseling. Women should be informed about the heightened risks of gestational diabetes, CS, PPH, and potentially rare but severe complications like retained placenta. Care during pregnancy and delivery should be individualized, ideally within a high-risk obstetric center,” wrote the authors.

This story was translated from Univadis Italy, part of the Medscape Professional Network.