Nowadays pathogenesis of preeclampsia is still unknown. Among the different etiological hypotheses, some authors proposed that it might be due to an abnormal immunologic response to foreign fetal antigen derived from the father's sperm. Indeed, the fetus is considered a semi allograft, being one half paternally derived in its antigenicity, and the first pathogenic insult of preeclampsia may be an abnormal maternal immune response towards this semi-allogenic implant. In the context of Artificial Reproductive Techniques, it has been shown that the use of donor and surgically retrieved spermatozoa (e.g. Testicular Sperm Extraction) increases the risk of preeclampsia, confirming the protective effect of sperm exposure on maternal complications.
Determining whether the lack of exposure to sperm antigens is associated with worse maternal and neonatal outcomes in pregnancies obtained through intracytoplasmic sperm injection after testicular sperm extraction for obstructive azoospermia.
Material and methods:
This is a single-center case-control retrospective study, focusing on all first pregnancies obtained through intracytoplasmic sperm injection after testicular sperm extraction for obstructive azoospermia at Humanitas Fertility Center between January 1st, 2010 and December 31st, 2019. Controls included patients that achieved their first pregnancy with intracytoplasmic sperm injection and ejaculated sperm, for a diagnosis other than azoospermia, in the same time period. Cases were matched with controls in a 1:2 ratio, considering female age, female BMI and year of controlled ovarian stimulation. The primary outcome measure was the delivery rate, defined as the number of deliveries divided by the total number of clinical pregnancies. Secondary outcome measures focused on maternal and neonatal complications, such as miscarriage rate, rate of main obstetric complications, prematurity rate and rate of congenital malformations.
By analyzing overall 113 pregnancies among cases and 214 pregnancies among controls, this study showed that the delivery rate was higher in controls with respect to cases (92.06% vs 84.07%, p = 0.026); among deliveries, live births were respectively 98.95% and 100%, while only one stillbirth occurred in cases. The first trimester miscarriage rate was higher in the cases than controls (13.27% vs 6.07%, p = 0.027), while no difference was found among rate of second trimester miscarriages, therapeutic abortions and ectopic pregnancies. There was no difference regarding the rate of maternal complications, including gestational hypertension, preeclampsia, HELLP syndrome, gestational diabetes, placenta previa, placental abruption and premature rupture of the membranes. Considering neonatal complications, it was shown that twins belonging to controls had a higher prematurity rate with respect to cases (65.79% vs 50.00%) but without a statistical relevance. Lastly, the rate of congenital malformations did not differ among the two groups.
This study showed that, once couples diagnosed with obstructive azoospermia achieve a pregnancy, they have a much higher risk of miscarriage in the first trimester in respect to non-azoospermic patients. Moreover, controls had a higher delivery rate in respect to cases; however, when the fetal status at birth was compared, no difference was found between live births and stillbirths.
Differently from the findings in the literature, no association with preeclampsia was found. This might be related to a collider bias/left truncation bias: since azoospermic patients are at higher risk of early termination of pregnancy, it results that they do not have the possibility to develop preeclampsia and other adverse outcomes. This article is protected by copyright. All rights reserved.