Reproductive outcome according to semen quality in couples with infertility problems

Abstract

Infertility problems may be due to both male and female factors. Some couples with infertility problems eventually conceive, and factors associated with infertility may also be associated with pregnancy complications and adverse birth outcomes (1Host E Lindenberg S Smidt-Jensen S The role of DNA strand breaks in human spermatozoa for IVF and ICSI.Acta Obstet Gynecol Scand. 2000; 79: 559-563Crossref PubMed Google Scholar). Thus, a less favorable outcome has been observed in pregnancies of previously infertile women (2Rowe P.J Conhaire F.H Hargreave T.B Mellows H.J WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press, Cambridge1993Google Scholar). Few studies have analyzed reproductive outcomes in offspring of couples with previous infertility problems caused by poor semen quality. To assess whether this group has an increased occurrence of adverse pregnancy outcome, a cohort of couples in which the man had undergone semen analysis for infertility was evaluated with respect to subsequent reproduction. By use of national identification numbers, data from the first semen sample of 5,180 males attending an infertility clinic in the county of Hordaland from 1976 to 1994 were linked with data on pregnancy outcome in the Medical Birth Registry of Norway (MBRN). The semen quality was dichotomized as normal (cell count >20 million/mL and percentage of normal cells >40%, WHO standard), or reduced (one or both of these criteria not fulfilled) (2Rowe P.J Conhaire F.H Hargreave T.B Mellows H.J WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge University Press, Cambridge1993Google Scholar). In this cohort, 2,302 males (44%) never fathered a child. Among the 5,368 children of the remaining 2,878 males, altogether 3,865 (72%) were born subsequent to the semen analysis and were included in the present study. Among these, 66 pregnancies represented twins, six were triplets, and one a quadruplet. Risks of a series of reproductive outcomes were assessed: male proportion, short gestational age (<260 days), low birth weight (<2,500 grams), perinatal death (stillbirths after 16 weeks of gestation and death during the first week of life), any birth defect, any serious birth defect, and Down syndrome. Reproductive outcomes in the observation group were compared to a reference group consisting of 10% of all births from 1976 to 1994 obtained from the MBRN. Because of an increased occurrence of multiple births in our cohort, singletons and twins were analyzed separately. Altogether 1,628 (42.1%) infants had fathers with reduced semen quality (RedSQ), whereas 2,237 (57.9%) had fathers with normal semen quality (NSQ). Among the 3,784 deliveries, 73 were multiple: 26 (1.6%) in offspring of RedSQ, and 47 (2.2%) in offspring of men with NSQ. In the same period the occurrence of multiple birth in the MBRN was 1.15%. Both NSQ and RedSQ related pregnancies had a reduced risk of pregnancy-induced hypertension compared with the reference group (Table 1 A similar tendency was observed for twin pregnancies. No deviant risks were observed for gestational diabetes or for placenta previa. Acute cesarean section was rarer in both groups and so was the use of vacuum extraction and forceps (Table 1). For twins similar results were observed (small numbers).Table 1Pregnancy outcomes in offspring (singletons) of fathers according to semen quality in West Norway, 1976–1994.legendIrgens. Semen quality and reproductive outcome. Fertil Steril 2001.OutcomeSemen qualityBirths (%)OR crude95% confidence intervalOR adjustedaAdjusted for year of birth, maternal age, and birth order.95% confidence intervalTotalReference group101,835Reduced1576Normal2135Male proportion (RR)Reference group52,4011.0051.5Reduced8030.990.94–1.0451.0Normal11191.020.98–1.0652.5Birth defectsReference group30961.001.003.0Reduced410.850.62–1.160.660.48–0.912.6Normal530.810.62–1.070.620.47–0.822.5Short gestational ageReference group56921.001.00(<260 days)5.6Reduced1151.231.01–1.491.150.94–1.407.3Normal1531.211.02–1.421.110.93–1.327.2Low birth weight (<2,500 g)Reference group42071.004.1Reduced731.120.89–1.430.950.74–1.214.6Normal1161.331.10–1.611.100.90–1.345.4Perinatal mortalityReference group11181.00(16 weeks +)1.1Reduced211.220.79–1.881.190.76–1.861.3Normal241.020.68–1.540.960.63–1.481.1Pregnancy-induced hypertensionReference group51511.005.1Reduced861.080.87–1.340.750.60–0.945.5Normal1101.020.84–1.240.710.58–0.875.2Abruptio placentaeReference group6801.000.7Reduced141.330.78–2.271.320.76–2.270.9Normal221.551.01–2.371.500.96–2.341.0Placenta previaReference group2371.000.2Reduced41.090.41–2.931.060.38–2.900.3Normal71.410.66–2.991.340.61–2.920.3Sectio, electiveReference group16941.001.7Reduced491.901.42–2.531.150.85–1.573.1Normal832.391.91–2.991.160.91–1.483.9Sectio, acuteReference group29571.002.9Reduced661.461.14–1.870.720.55–0.954.2Normal1161.921.59–2.320.810.65–0.995.4VacuumReference group40341.004.0Reduced540.860.65–1.130.210.16–0.283.4Normal630.740.57–0.950.170.13–0.233.0ForcepsReference group34981.003.4Reduced831.561.25–1.950.300.24–0.395.3Normal1321.851.55–2.220.370.30–0.456.2a Adjusted for year of birth, maternal age, and birth order.legend Irgens. Semen quality and reproductive outcome. Fertil Steril 2001. Open table in a new tab NSQ twins had an increased risk of low birth weight (OR 1.80, CI 1.14–2.85); in RedSQ twins and singletons the risk of low birth weight was not increased. Perinatal mortality in the two groups was not increased. In both groups, the occurrence of birth defects was reduced (see Table 1) whereas the occurrence of Down syndrome and the male proportion did not differ from the reference group. Similar results were observed for twins (small numbers). The main result of the present study is reassuring: maternal and paternal factors related to infertility are hardly reflected in the outcome data. However, in previously infertile couples, the potentially increased risks of adverse pregnancy outcomes might, to an unknown extent, be counteracted by increased maternal caution, good pregnancy care, and high quality health services at birth. Thus, both infertility groups may have benefited from a higher level of care. The lower birth weight in NSQ-related twins is compatible with infertility originating in the mother, and might be related to ovulation stimulation, in vitro fertilization (IVF), and other therapy. Likewise multiple births were more frequent when the infertility problem most likely originated in the mother. However, a higher percentage of multiple births was also seen in the offspring of men with reduced semen quality. The reduced occurrence of birth defects in both groups might be attributable to an early prenatal diagnosis with subsequent termination not reported to MBRN. However, as most of the births occurred before these procedures were introduced, this explanation hardly accounts for the finding. No data were available for determining which of the births occurred after hormonal stimulation or IVF, but obviously some births, probably a small subset, are related to assisted fertilization. Thus, the multiple birth rate was increased both in NSQ (2.2%) and in RedSQ (1.6%) pregnancies; but it was still far lower than the multiple birth rates reported after IVF during the years 1988 to 1991 (30%) (3Annual report 1998. Medical Birth Registry of Norway. Bergen, Norway: University of Bergen, 1999.Google Scholar). The reduced birth weight in NSQ-twins was not consistent with the nonreduced birth weight among IVF twins (4von Düring V Maltau J.M Forsdahl F Abyholm T Kolvik R Ertzeid G et al.Pregnancy, birth and infants after in-vitro-fertilization in Norway, 1988–1991.Tidsskr Nor Laegeforen. 1995; 115 ([in Norwegian]): 2054-2060PubMed Google Scholar). On the other hand, among IVF singletons, contrary to the present study, adverse pregnancy outcomes were reported for gestational age, birth weight, perinatal mortality, and pregnancy-induced hypertension (4von Düring V Maltau J.M Forsdahl F Abyholm T Kolvik R Ertzeid G et al.Pregnancy, birth and infants after in-vitro-fertilization in Norway, 1988–1991.Tidsskr Nor Laegeforen. 1995; 115 ([in Norwegian]): 2054-2060PubMed Google Scholar). Whether these increased risks might be attributable to the cause of infertility or to the medical procedures has been difficult to ascertain. However, the results of the present study suggest that male, and possibly female, infertility per se might not be associated with increased risks of adverse perinatal outcome in subsequent pregnancies.