Update on: a meta-analysis of sperm donation offspring health outcomes – 2018 update

Abstract

Dear Editor, In 2017 our team published a meta-analysis on the health outcomes of offspring conceived from donor sperm.1 At the time of this review, there were only eight studies that were eligible for inclusion, and only three qualified for meta-analysis, 2-4 and only two studies provided data for each outcome analysis. Our review demonstrated the paucity of studies investigating the perinatal outcomes of sperm donation.After identifying this gap in research, we undertook a population study comparing the perinatal outcomes for neonates conceived with donor sperm and those conceived spontaneously in the state of South Australia.5 Furthermore, since the census date of the metaanalysis a further two studies have been published that also meet the criteria of our original review, 6,7 and we believed it was important that we add these three studies (two by other authors and one by ourselves), to our meta-analysis to see if the original findings were either supported or refuted.The original findings showed that; donor sperm neonates in comparison to naturally conceived neonates were not at increased risk of being born of low birth weight [risk ratio (RR): 1.04, 95% confidence interval (CI): 0.86-1.25, P-value (P) = 0.71, I 2 = 0%]; preterm (RR: 0.91, CI: 0.75-1.12, P = 0.38, I 2 = 0%); or with increased incidences of birth defects (RR: 1.20, CI: 0.97-1.48, P = 0.09, I 2 = 57%). 1The addition of the new studies allowed not only for an increase in the number of studies included in the meta-analysis conducted above but also for a larger range of perinatal outcomes. All data extraction and analysis followed the method described in our original review. The studies that were included in each meta-analysis are listed as reference numbers in superscript after each meta-analysis.The updated meta-analysis has demonstrated that, in comparison to naturally conceived neonates, donor sperm neonates were at increased risk of being born of low birth weight (RR: 1.17, CI: 1.03-1.33, P = 0.02, I 2 = 52%), [3][4][5][6][7] and with increased incidences of birth defects (RR: 1.30, CI: 1.05-1.59, P = 0.01, I 2 = 72%) (Fig. 1). 2,4,6 However, they were not at increased risk of being born preterm (RR: 1.05, CI: 0.91-1.21, P = 0.47, I 2 = 52%), [3][4][5]7 very preterm (<32 weeks) (RR: 1.17, CI: 0.75-1.81, P = 0.49, I 2 = 0%), 5,7 very low birth weight (<1500 g) (RR: 1.22, CI: 0.76-1.97, P = 0.4, I 2 = 0%), 5,7 small for gestational age (birth weight <10th percentile) (RR: 1.19, CI: 0.99-1.42, P = 0.06, I 2 = 82%), 5,7 large for gestational age (birth weight > 90th percentile) (RR: 1.04, CI: 0.86-1.38, P = 0.71, I 2 = 0%), 5,7 with altered perinatal mortality (RR: 0.93, CI: 0.59-1.45, P = 0.74, I 2 = 0%), 5,7 of lower mean birth weight (mean difference −12.5 g, CI: −32.03 to 7.02 g, P = 0.21, I 2 = 0%), 3,[5][6][7] or of lower mean gestational age (mean difference −0.02 weeks, CI: −0.10 to 0.05 weeks, P = 0.55, I 2 = 12%). 5,7

Self-reported physical health status of donor sperm-conceived adults

“…56,57 Evidence shows that donor-conceived neonates also experience similar poor perinatal outcomes. [20][21][22][23][24][25] However, those common adult outcomes of cardiovascular disease (including hypertension and other cardiovascular outcomes) and type 2 diabetes were not observed in the responses of the donor-conceived adults in this study. Furthermore, not only did the donor sperm-conceived group not have a significant increase in bodyweight or BMI as suggested through the DOHaD theory but actually reported a significantly lower BMI.…”

“…Moreover, the selfreports are consistent with the increased incidences of birth defects associated with donor sperm treatment. 25 This study highlights that there is a group of people conceived through reproductive medicine that self-reported worse adulthood health outcomes than their spontaneously conceived peers. Confounding of multiplicity and maternal complications, which can include preeclampsia, can be directly associated with the fertility treatment that their mother received.…”

“…The questionnaire was completed anonymously on the SurveyMonkey website and was live for four months between the start of December 2017 and the end of March 2018. Questions were developed based on known DOHaD adult health outcomes associated with the perinatal outcomes of donor conception, [21][22][23][24][25] as well as other questions developed by the authors using their experience to cover a wide range of physical and mental health outcomes. The questions covered the following categories: demographics, information regarding birth (such as whether participants were donor conceived), general health [including outcomes such as body mass index (BMI), exercise levels and alcohol usage], cardiovascular, chromosomal and genetic, dermatological, EENT (ears/eyes/nose/throat), endocrinological, gastrointestinal, immunological, musculoskeletal, neurological, oncological, reproductive, respiratory, urogenital and mental health questions (mental health outcomes are described in the companion article).…”

“…One recent meta-analysis showed that sperm donation neonates were significantly more likely to be born of LBW and with more birth defects than those conceived spontaneously. 25 However, an earlier review (non-systematic and without meta-analysis) suggested that the perinatal outcomes were comparable to those spontaneously conceived. 26 Uncertainty remains due to the lack of systematic reviews and meta-analysis, as well as the low number of studies that met the inclusion criteria and were then able to be included in the meta-analysis of donor sperm perinatal outcomes.…”

“…26 Uncertainty remains due to the lack of systematic reviews and meta-analysis, as well as the low number of studies that met the inclusion criteria and were then able to be included in the meta-analysis of donor sperm perinatal outcomes. 25 The long-term health of donor-conceived people continues to be of concern and therefore warrants further investigation.…”