The interaction effect between advanced paternal age and paternal obesity is associated with the low implantation rate in couples with unexplained recurrent pregnancy loss

Abstract

ObjectiveTo explore the roles of advanced paternal age (APA) and abnormal paternal weight on embryo quality and pregnancy outcomes for unexplained recurrent pregnancy loss (uRPL) couples who underwent preimplantation genetic testing for aneuploidies (PGT-A).MethodsThis study included 779 uRPL couples who underwent their first PGT-A cycles between 2014 and 2018. Male patients’ aging and nutritional status were quantified by paternal age and body mass index (BMI). Routine semen parameters and sperm DNA fragmentation index (DFI) were used to reflect the seminal quality. Blastocyst formation rate and aneuploidy rate were used to reflect the embryo quality. Cycle cancellation rate, implantation rate, pregnancy loss rate, and live birth rate were measured to evaluate the treatment efficiency from IVF. To remove the interference of maternal age, only the women younger than 38 years old were included. After univariate screening, interaction tests were performed in a generalized linear model (GLM) to further examine the effects of paternal age and BMI on each outcome indicator.ResultsIn the total population (779 cycles), there were no statistical differences in aneuploidy rate, cycle cancellation rate, implantation rate, pregnancy loss rate, and live birth rate, whether stratified by paternal age or paternal BMI. Similar results occurred in the younger men (<40 y.o., 633 cycles). Conversely, among the men with advanced age (≥40 y.o., 146 cycles), there were statistical differences between the three BMI groups in four semen parameters (total sperm number, total motility, progressive motility, and total motile sperm count), implantation rate, and live birth rate. After interaction testing, the results of GLM suggested that the interaction effect between APA and paternal obesity was associated with the low implantation rate of uRPL couples.ConclusionsFor the uRPL couples seeking for PGT-A treatment, if the male patients have both advanced age and obesity, their spouses are at higher risks for embryo implantation failure.

A Mini-Review Regarding the Clinical Outcomes of In Vitro Fertilization (IVF) Following Pre-Implantation Genetic Testing (PGT)-Next Generation Sequencing (NGS) Approach

“…Illumina twelve with MiSeq [ 11 , 13 , 14 , 16 , 24 , 27 , 29 , 33 , 34 , 38 , 43 , 44 ]; three with HiSeq [ 15 , 28 , 32 ]; two with NextSeq [ 31 , 41 ]; one with sequencing-by-synthesis [ 45 ]; …”

“…Following the allocation of the articles that met the eligibility criteria, we extracted several strong points: The body mass index (BMI) and obesity influence the chances of implantation and amplify the risk of miscarriage [ 40 , 46 ], also dependent on the couple’s age [ 27 ], cesarean section (C-section) [ 22 ], and ovarian reserve [ 23 ], rather than correlated with previous unsuccessful pregnancies [ 36 ]; While age exerts a detrimental effect, it is mitigated through SNP-based PGT-A [ 39 ], and the embryos’ morphology possesses a significant threat with greater impact [ 11 , 37 , 47 ], but contradicted on several occasions [ 21 , 29 , 38 ]; Embryo morphokinetic [ 11 , 34 , 37 ] and inner cell mass (ICM) morphology constitute an optimal predictor of sustained implantation [ 48 ]; Mitochondrial DNA (mtDNA) copy numbers are higher in day 5 blastocysts of older women than day 6 blastocysts, further associated with a low chance of ongoing pregnancies [ 14 , 24 ]; The content of mtDNA is unable to predict the miscarriage risk [ 12 ] and additionally refuted when comparing the outcome differences between them [ 19 ] despite the cryo-storage [ 49 ]; Despite the sensitivity of platforms, errors still might occur, and their optimization is mandatory; PGT-NGS significantly improves the clinical outcomes in mosaic embryos [ 28 , 41 , 50 ], FAST-SeqS being a reliable and scalable PGT-A method [ 15 ]; Mosaic embryos have poor reproductive potential but retain the ability to result in live births [ 13 , 33 ], further sustaining that TE biopsy did not add detectable adverse effects [ 42 ] but as a supplement for the management of recurrent implantation failure (RIF) [ 45 ...…”

“…The body mass index (BMI) and obesity influence the chances of implantation and amplify the risk of miscarriage [ 40 , 46 ], also dependent on the couple’s age [ 27 ], cesarean section (C-section) [ 22 ], and ovarian reserve [ 23 ], rather than correlated with previous unsuccessful pregnancies [ 36 ];…”

“…There is no relationship between BMI and ploidy, but rather upon semen morphology [ 27 ] of the embryo with the mention that the live birth rate can be low to the detriment of high miscarriage rate in obese patients [ 40 , 46 , 58 ] per BMI classification issued by the World Health Organization (WHO). The BMI and serum P4 had an insignificant impact on the copy number.…”