LISBON (FRONTLINE MEDICAL NEWS) – A large observational study found no increased risk of preterm birth or low birth weight following in vitro fertilization within acceptable limits of ovarian stimulation compared with unstimulated IVF.

“These findings support that ovarian stimulation is safe for maximizing live birth rates when you use acceptable limits of ovarian stimulation such as less than 20 oocytes,” Dr. Sesh Kamal Sunkara said at the annual meeting of the European Society of Human Reproduction and Embryology.

Epigenetic modifications resulting from ovarian stimulation or embryo culture are under increasing scrutiny as possible contributory factors to adverse perinatal outcomes.

A recent analysis of almost 66,000 singleton births by Dr. Sunkara and her associates showed a significantly higher risk of preterm birth (PTB) and low birth weight (LBW) in women with an excessive response (> 20 oocytes) to ovarian stimulation versus those with a normal response (10-15 oocytes) (Hum. Reprod. 2015; 30:1473-80).

A 2013 systematic review and meta-analysis also identified a higher risk of PTB and early PTB among singletons born after blastocyst- versus cleavage-stage embryo transfer in IVF (Fertil. Steril. 2013; 100: 1615-21.e10).

Both of these confounding factors were taken into account in the current analysis, reported Dr. Sunkara , of Aberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Scotland.

Using the Human Fertilisation and Embryology Authority database, which includes data for all IVF cycles performed in the United Kingdom from 1991 to 2012, the investigators examined 719,220 fresh IVF stimulated cycles and 135,570 fresh IVF unstimulated cycles, resulting in 105,374 and 10,668 singleton live births, respectively. Surprisingly, most women in either group were aged 18-34 years at the time of treatment, Dr. Sunkara said.

A large proportion of the unstimulated cycles did not have any oocytes retrieved compared with the stimulated group (41.7% vs. ~7%).

The overall birth rate per cycle was significantly higher with stimulation than without stimulation (19.4% vs. 8%), as was the multiple birth rate (24.4% vs. 2.1%), she said.

In the unadjusted analyses, the stimulated versus unstimulated group had significantly higher rates of PTB (9.2% vs. 5.5%; odds ratio, 1.72; 95% confidence interval 1.58-1.88), early PTB (1.7% vs. 0.7%; OR, 2.36; CI, 1.88-2.96), LBW (9.3% vs. 5.1%; OR, 1.91; CI, 1.75-2.09), and very LBW (1.8% vs. 0.8%; OR, 2.23; CI, 1.80-2.77).

No significant differences were observed, however, for each outcome between stimulated and unstimulated cycles following logistic regression and adjustment for maternal age, year of treatment, previous IVF cycles, previous live birth, number of oocytes retrieved (≤ 20 or > 20), and day of embryo transfer (cleavage or blastocyst stage), Dr. Sunkara said.

The adjusted odds ratios were: PTB (aOR, 1.04; C.I. 0.60-1.80), early PTB (aOR, 1.60; C.I. 0.51-5.01), LBW (aOR, 1.93; C.I. 0.95-3.94), and very LBW (aOR, 1.01; C.I. 0.55-4.22).

“The results demonstrated that safe stimulation within acceptable limits does not increase the risk of PTB and LBW,” she said.

Dr. Sunkara reported no having no financial conflicts.