Interpretation
Evidence shows that conception after IVF/ICSI increases the odds of preterm delivery when analysed in population-based cohorts4,5,22-24. Contrary to those findings, in our cohort of infertile women with singleton pregnancy after reproductive surgery, IVF/ICSI, compared to spontaneous conception, did not increase the odds of preterm delivery. Still, there are few reports on an outcome of spontaneous conception after reproductive surgery due to an opinion that reproductive surgery should only be performed as an initial part of infertility treatment before proceeding to IVF/ICSI9. Nevertheless, encouraging reports on a high spontaneous pregnancy rate after reproductive surgery, as in this study, emerged in the last years8,10. Similar to our finding, Boyle et al.8 have found the low preterm delivery rate in women who conceived spontaneously after restorative reproductive medicine after failed IVF. Indeed, waiting for spontaneous conception in infertile women who are often at advanced reproductive age is discouraging. However, besides lower treatment burden for women and lower medical expenses, an essential advantage of a spontaneous conception after reproductive surgery is a lower rate of multiple pregnancies compared with IVF/ICSI, which was evident in our cohort. Precisely lowering the multiple pregnancy rate is the only preventive measure that we can take to reduce preterm delivery risk in women who need an infertility treatment25.
We report that reproductive surgery in infertile women had no significant effect on preterm delivery, regardless of the mode of conception. However, Valenzuela-Alcaraz et al.26 have found the significantly higher prevalence of overall pregnancy complications in all studied infertility groups regardless of the infertility treatment, preterm delivery being the highest in the IVF/ICSI group. Also, Dunietz et al.6, when compared spontaneous conception with assisted reproductive techniques (ART) conception in women with singleton pregnancy after infertility treatment, have reported an increased preterm delivery risk after ART within each of the treatment group. However, compared with women who had trouble conceiving but conceived without any assistance, Oberg et al.27 had reported that when women received some fertility treatment, the odds of preterm delivery were higher through independent multiple gestations. All mentioned studies have evaluated a relative relationship between infertility treatment and preterm delivery using multivariate regression models, which have well-documented limitations as a means to explore causal relationships28. In our study, using the propensity score method, fertile women and women who received infertility treatment were well balanced not only for every single risk factor for preterm delivery but also for the number of co-existing risk factors per woman. Considering this, our finding that reproductive surgery had no significant effect on preterm delivery in the well-balanced sample suggests that the higher rate of women with co-existing risk factors in infertile women may be the main contributor to an increased risk of preterm delivery when compared with all fertile women.
In our study, the main indication for infertility treatment was endometriosis, in one-third of the women, which might contribute to our insignificant treatment-related side effect. Namely, Stern et al. have reported that among all ART deliveries, following singleton or multiple pregnancies, the increased preterm delivery risk was associated with male factor, ovulation disorders, tubal inflammation, but not with endometriosis7.
Our findings do not contradict other findings that, compared with all fertile women, preterm deliveries are higher in women who conceived after IVF/ICSI or received any infertility treatment29. What our study pointed out is that not the mode of conception or reproductive surgery, but rather maternal risk factors for preterm delivery like high maternal age, nulliparity, and chronic diseases, which were more prevalent in women who received infertility treatment and even more prevalent in women who conceived after IVF/ICSI might contribute to the higher prevalence of preterm delivery when compared to all fertile women. Besides, to our finding, the higher prevalence of co-existing risk factors for preterm delivery per woman may be the most critical contributor to the higher rate of preterm delivery in women who received infertility treatment.