The number of pregnancies after ART is still increasing and there is some data showing that IVF/ICSI is associated with a higher rate of complications with regard to both the course of pregnancy and neonatal outcome. Of note, the potential negative impact of micromanipulation techniques should be considered, but only a few research studies have made precise distinctions between IVF and ICSI pregnancies [11, 12, 14].
Therefore, we systematically analyzed and compared 334 pregnancies and 530 children after IVF and ICSI, and discovered that the course of pregnancy is more complicated in IVF pregnancies (leading to more frequent maternal hospitalizations), whereas the primary fetal outcome (i.e., APGAR value after one minute and the necessity for admission to a NICU) seems to be better in this group than after ICSI treatment.
The significant association between IVF pregnancies and premature rupture of membranes, premature uterine contractions, and cervical insufficiency could be seen as concordant with the results of a smaller study that reported an increased preterm delivery risk in IVF versus ICSI-conceived pregnancies . Mean gestational age at the time of delivery, however, did not differ between the two groups in our study, which supports data from Bonduelle et al., who found no disproportion in preterm delivery between pregnancies after the two major methods of ART. Preeclampsia, recently linked with decreased ovarian reserve , was not found to be overrepresented in our IVF group, although one might have suspected a relation between female subfertility (not male subfertility, leading to ICSI) and decreased ovarian reserve, and therefore, preeclampsia.
There were significant differences between the groups concerning gestational age, fetal birth weight, and mean APGAR levels, with lower levels for all variables in the ICSI group. Moreover, children in this group had to be admitted to the NICU more often.
A plausible explanation for this phenomenon is lacking; one might, however, speculate that early manipulation of the egg cell for ICSI could have a long-term negative impact.
When analyzing age groups, we found the risk of preterm delivery to be higher after ICSI treatment, but the fact that this observation no longer existed when focusing only on singleton pregnancies led to the conclusion that this might be predominantly due to multiple gestations within the ICSI group. Of note, the average gestational age in multiples was significantly lower in the ICSI group compared to the IVF group; this was not true of singleton pregnancies, as shown in Tables 5 and 6.
Concerning major fetal malformations, there was no statistically significant difference between the two groups, which is in accordance with other studies [14, 16, 17]. Wen et al. recently performed a meta-analysis that included more than 124000 ART pregnancies , and found no difference in the risk for malformations between children conceived by IVF and/or ICSI, although ART-conceived pregnancies were generally at increased risk for birth defects, compared to naturally conceived pregnancies (OR: 1.37). This is in line with the results of Pinborg et al., who suspected subfertility per se as a major risk factor for adverse perinatal outcomes after ART . The fact, however, that, even in the same mother, an ART singleton has a poorer outcome than a non-ART sibling, leads to the presumption that factors related to the hormonal stimulation, embryo culture, or cryopreservation may also have a potentially negative impact on the offspring. In contrast, a smaller case-controlled study revealed no increase in congenital malformations in ICSI-conceived pregnancies compared to naturally conceived pregnancies —possibly because of the small sample size.
A Chinese study analyzing birth defects in over 15400 children after ART found that the distribution of birth defects reflects the distribution in the general population, while the total frequency of birth defects was not significantly higher within the ICSI group, compared to insemination or conventional IVF .
In our ICSI group, there was one case of a heart malformation and two cases of facial malformation, and, in the IVF group, two cases of heart malformation, one case of facial malformation, and one case of omphalocele combined with malformation of the limbs.
Notably, the number of children after ICSI was unusually low (15%) in our collective. A possible explanation could be that all women whose data were analyzed in the present retrospective study were referred to our tertiary care center by their gynecologist for a distinct reason (e.g., multiple pregnancy, advanced maternal age, desire for first-trimester screening, wish for a second opinion concerning the mode of delivery), and women who undergo an ICSI procedure, typically performed for male subfertility, might be younger and more healthy, and therefore, less often referred to a tertiary care unit. However, age, BMI, and pre-existing diseases, such as hypertension, did not differ between the two groups in our study.
We have to admit, however, that the disproportionate underrepresentation of ICSI is an obvious limitation of our study.
Moreover, the “origin” of sperm for ICSI (ejaculated/frozen/after testicular sperm extraction/after epididymal sperm aspiration) was unfortunately not systemically noted in our data. A recent cohort study revealed, however, that the above-mentioned methods of operative sperm collection seem to be as safe as conventional ICSI, IVF, and natural conception with regard to neonatal outcome, including congenital malformations .
Another possible limitation of our study is the lack of an age-matched control group.
We decided, however, against creating a control group from our high-risk collective at the University clinic (only a few uncomplicated pregnancies are treated at our center) in order to avoid comparing one high-risk collective (e.g., women after preterm delivery or premature rupture of membranes in a past pregnancy), with another (St. p. ART) and preferred to use data concerning uncomplicated pregnancy outcomes from low-risk collectives reported in the literature.