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Full AJOG Editor’s comment: Prof. Yves Ville: Is the due date becoming overdue ?

(Editor’s comment relates to the 3 AJOG articles below: Gibson et al, Melamed et al & Masoudian et al)

In vitro fertilization using egg donation  (ED) is being used increasingly for women requiring assisted reproduction techniques (ART) with a delivery rate per transfer of around 40%. Initially designed to overcome infertility in young women with hypergonadotropic hypogonadism, this technique is now also increasingly used to achieve pregnancy in older women.

Multiple studies have documented that ED pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental dysfunction, including small for gestational age, and preterm delivery. However, multiple gestations, advanced age, and underlying polycystic ovary syndrome are constant confounding factors for all studies examining the association between assisted reproductive techniques (ARTs) and hypertensive disorders in pregnancy.

In the March issue of AJOG, Masoudian et al. have reviewed the evidence for an increased risk of preeclampsia or gestational hypertension following ART with ED. Their metaanalyisis is based upon 19 studies covering over 86,000 pregnancies. They confirm that ART using ED is associated with an increased risk of both gestational hypertension and pre-eclampsia, independently from maternal age and multiple pregnancies, when compared to both spontaneous and ART pregnancies without ED. In addition, oocyte recipients have been reported to be at an increased risk for gestational diabetes, first- and second-trimester bleeding, cesarean delivery, and preterm delivery compared with patients undergoing IVF and the general population. IVF parameters such as the age of the oocyte donor, egg quality, the number of embryos transferred, and the cause of infertility or the reason for use of donor oocytes are not accounted for and might have a significant impact on pregnancy outcome. There is still almost no information in the literature on the long-term complications of ED pregnancies for the mother.

In vitro fertilization provides an interpretative model to assess the role of fetal antigenicity in the development of placental pathologies. The success of pregnancy depends upon an appropriate implantation and placental function. Any insult during the process of implantation and placentation leads to obstetrical complications, including spontaneous miscarriage, SGA, preterm birth, and PET. Studying the obstetric outcome of donor egg IVF pregnancies may help uncover the immunological mechanisms involved in pre-eclampsia, because the entire fetal genome is allogenic in these pregnancies.

DO pregnancy should be considered as high risk pregnancies including hypertensive disorders of pregnancy, SGA, preterm delivery, and caesarean section.

Women should be informed about these risks before undergoing DO-assisted conception. These women should be managed in high-risk obstetric clinics with appropriate monitoring and management strategies to reduce complications. The use of serial growth scans in DO pregnancies needs further evaluation.

These pregnancies may well be particularly prone to the late and steep increase risk of pregnancy induced hypertension. Expectant management of pregnancies at term is not without risk including, increased fetal deaths, increased cesarean delivery, and neonatal and maternal morbidities.

In this month's issue of AJOG, Gibson et al. examined the incidence of hypertensive disorders of pregnancy for women who were expectantly managed at term by week of gestation. They found that the risk of developing any hypertension in expectantly managed women was 4.1% after 37 weeks, 3.5% after 38 weeks, 3.2% after 39 weeks, and 2.6% after 40 weeks. These results have to be looked at with the increasing evidence that induction of labor from 39 weeks’ onwards is unlikely to increase the risk of cesarean section  nor that of neonatal morbidity. This is likely to call for an extensive re-evaluation of the duration of pregnancy ; especially so with the increasing part of ART in human conception, especially following on OD and the ever growing prevalence of gestational diabetes. Indeed in the same issue of AJOG, Melamed et al. show that in women with gestational diabetes mellitus, the routine induction of labor at 39 weeks is associated with a lower risk of cesarean delivery compared with expectant management.  

Term is no longer the safest port to sail to for an increasing number of pregnancies and surveillance in the third trimester probably needs to be re-assessed in appropriately designed interventional studies.


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Commentaries by Editor Prof. Jim Thornton