Birth defects after a history of subfertility: a registry-based case-control study in the Northern Netherlands

Bos, M.E. (2013) Birth defects after a history of subfertility: a registry-based case-control study in the Northern Netherlands. thesis, Medicine.

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Abstract

Background: In children conceived via assisted reproduction, an increased overall risk for birth defects has been described in literature. In these newborn, a specific increase has been reported for cardiovascular, musculoskeletal, urogenital and gastrointestinal abnormalities. It remains uncertain, however, whether the rise in occurrence of birth defects can be attributed to patient characteristics related to subfertility, or to the treatment itself. The primary aim of the study is to evaluate whether specific types of birth defects occur more often in offspring of subfertile couples rather than in the offspring of fertile couples. The secondary aim is to evaluate when birth defects are more likely to develop: after a history of subfertility compared to the offspring of couples who received in vitro fertilization (IVF) or intracytoplasmatic sperm injection (ICSI). The tertiary aim is to evaluate whether prolonged time to pregnancy (TTP) in the group of subfertile couples shows a positive correlation with regard to the prevalence of specific types of birth defects. Methods: For performing this case-control study we used data from EUROCAT – Northern Netherlands, a registry of birth defects. 4392 cases and 1456 (malformed) controls were identified. These subjects were born between 1997 and 2010, and were registered by EUROCAT. The cases were children and fetuses with major birth defects of a non-genetic origin. Controls were defined as children and fetuses with a chromosomal anomaly, a microdeletion or a monogenic anomaly. In the statistical analysis, three groups of children and fetuses were compared: Sub-NC (n=296), IVF/ICSI (n=174) and children and fetuses of fertile couples (n=5378). Results: Compared with fertile women, Sub-NC women were at an increased risk of having a child with a penoscrotal hypospadia (adjusted odds ratio [aOR]: 6.80; 95% confidence interval [CI]: 2.35 – 19.63). Subfertile women conceiving via IVF/ICSI were at an increased risk of having a child with a limb anomaly (aOR: 2.80; CI: 1.51 – 5.20), especially polydactyly (aOR: 5.26; CI: 2.47 – 11.20). Compared to fertile women, the entire group of subfertile women (Sub-NC and IVF/ICSI) was at an additional increased risk of having a child with an epispadia (aOR: 4.28; CI: 1.04 – 17.57) and cystic kidneys (aOR: 2.10; CI: 1.02 – 4.34). Surprisingly, Sub-NC women showed a significant decreased risk for having a child with a congenital anomaly in general, considering congenital anomalies occurring in all groups. Overall, a significantly decreased risk of having a child with a congenital hip dysplasia was seen in subfertile women, as was also described for the Sub-NC women alone. Conclusions: In this study, Sub-NC women were at an increased risk of having a child with specific major congenital anomalies, especially penoscrotal hypospadias. The results of this study may be of great importance for public health, since subfertility is a growing health issue since women are conceiving at older ages.

Item Type:	Thesis (Thesis)
Supervisor name:	Supervisors: and Walle, dr. H.E.K. de dept GENETICS UMCG and Hoek dr. A. dept OBGYN UMCG and Haadsma dr. M.L. dept GENETICS UMCG
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:52
Last Modified:	25 Jun 2020 10:52
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1323

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