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.