Effect of male age on pregnancy and neonatal outcomes in the first frozen-thawed embryo transfer cycles of IVF/ICSI treatment
A retrospective cohort study was conducted to evaluate the effect of male age on reproductive and neonatal outcomes in couples following IVF/ICSI treatment.
Past study results remain controversial with differing selection criteria, analytical methods and neglect in accounting for female age bias.
This study utilised anonymised data from 32,320 first FET (frozen embryo transfer) cycles carried out at 2 centres for Assisted Reproduction within Jiao Tong University and Tongji University.
Inclusion criteria filtered data for: embryo transfers in first IVF/ICSI cycle, women aged 20-35 years old, with BMI between 18.5 to 25, normal ovarian reserve (FSH < 10 IU/L) and antral follicle count on cycle day 3, who only used freshly ejaculated spermatozoa.
IVF/ICSI cycles that used preimplantation genetic diagnosis (PGD), in vitro maturation (IVM), donor oocyte or sperm, were excluded from the study along with women featuring high blood pressure, diabetes, heart, thyroid, uterine abnormality, or other diseases that would bias ART or pregnancy outcomes.
In this study, clinical pregnancy was defined by the presence of a gestational sac inside the uterus at 6 gestational weeks, with biochemical pregnancy as serum β-hCG > 10 mIU/ml and miscarriages as a miscarriage before 22 weeks. The delivery of one or more infants, with any signs of life, after 36 weeks gestation was classified a live birth. However, a live birth before 37 or 32 weeks gestation was defined as, preterm birth (PTB) or early preterm birth (EPTB), respectively. Low birth weight (LBW) and very low birth weight (VLBW) was a birth weight <2500g or <1500g respectively, while foetal macrosomia is a birth weight ≥ 4000g.
IVF or ICSI was performed according to semen quality. Fertilisation was checked 16 to18 hours following insemination/microinjection. On day 3 of embryo culture, embryos were graded by morphological assessment, with only good-quality embryos (6 or more blastomeres, ≤ 20% fragmentation) selected for cryopreservation. Residual embryos were the transferred to blastocyst media for further development and assessed again on day 5 or 6 using the Gardner criteria followed by cryopreservation.
Endometrial preparation protocols: natural monitoring, artificial cycle, or ovarian stimulation cycle were selected according to patients clinical indications. No more than 3 (before 2015) and 2 (after 2015) good quality embryos were transferred with luteal (progesterone) support until hCG test 14 days after transfer. Two weeks later, patients with a positive hCG result underwent a ultrasonography to confirm clinical pregnancy.
After inclusion exclusion filtering of data, a total of 5512 FET cycles was analysed in this study.
Male age groups were divided accordingly; < 31, 31-35, 36-40, 41-45, > 45. Mean male age was 28.92, 33.15, 37.34, 42.45 and 49.59 in each group respectively with mean female age in these same groups; 29.38, 32.24, 33.88, 33.93 and 33.36 respectively.
Baseline characteristics showed mean female BMI did not differ significantly across the 5 groups (P > 0.2) while the majority of embryo transfers was two embryos (87.8%) and day 3 cleavage stage embryos (91.7%).
Initial analysis of outcomes found no significant difference in the rate of biochemical pregnancy, clinical pregnancy, live birth, miscarriage and ectopic gestation although embryo implantation rate was significantly higher comparing the youngest to oldest groups (40.93 vs 36.64%).
Advanced statistical analysis showed little change, both odds ratio and adjusted odds ratio, between male age and clinical outcomes with only a slight (non-significant) trend towards lower probability of clinical pregnancy and live birth in the oldest (> 45) group.
Finally analysis of neonatal outcomes, in babies born following the first FET cycle, identified no difference in preterm birth, gestational age, birth weight and neonatal malformations between the male age groups.
Breakdown analysis of neonatal malformations according to type and age groups found that malformations of the circulatory system (27 in 1820 births) was the most common, across all age groups, suggesting babies born through ART may have a higher risk of circulatory system defects.
SUMMARY: DOES MALE AGE AFFECT IVF SUCCESS
In this largest study of male age on IVF / ICSI success, no significant difference was found in clinical pregnancy or live birth rates (P > 0.2), among the 5 male age groups; <31, 31-35, 36-40, 41-45, >45, however implantation rate was statistically higher in <31 vs >45 age groups (40.9 vs 36.6 %).
- Retrospective study type
- Small sample size of men > 45
- Study population of single ethnicity
Wu Y, et al. (2016). Effect of Paternal Age on Reproductive Outcomes of Intracytoplasmic Sperm Injection. https://doi.org/10.1016/s0015-0282(16)58450-7
Duran E H, et al. (2010). Impact of male age on the outcome of assisted reproductive technology cycles using donor oocytes. https://doi.org10.1016/j.rbmo.2010.03.005
Campos I, et al. (2008). Effects of men and recipients’ age on the reproductive outcome of an oocyte donation program. https://doi.org10.1007/s10815-008-9255-9
Frattarelli J L, et al. (2008). Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. https://doi.org10.1016/j.fertnstert.2007.06.009
de La Rochebrochard E, et al. (2006). Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France. https://doi.org/10.1016/j.fertnstert.2005.11.040
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