Cozzolino Mauro, Pellegrini Livia, Ottolini Christian Simon, Capalbo Antonio, Galliano Daniela, Pellicer Antonio
IVIRMA Global Research Alliance, IVI Bologna, Bologna, Italy.
IVIRMA Global Research Alliance, IVI Roma, Rome, Italy.
Hum Reprod. 2025 May 13. doi: 10.1093/humrep/deaf080.
Do severely impaired sperm concentrations (oligozoospemia) in male factor infertility affect embryo aneuploidy rates and clinical results after IVF oocyte donation cycles?
Severe oligozoospermia (SO) in IVF cycles utilizing donor oocytes does not significantly affect embryo euploidy rates or IVF outcomes or cumulative live birth rates (CLBRs).
SO has previously been linked to elevated rates of chromosomal abnormalities in spermatozoa and altered rates of embryo development with poorer reproductive outcomes. Nonetheless, the precise impacts of severe male factor infertility on embryonic aneuploidy rates and the success of IVF, in the context of controlled female ages in oocyte donation cycles with preimplantation genetic testing for aneuploidy (PGT-A), are still not fully understood.
STUDY DESIGN, SIZE, DURATION: This retrospective observational cohort study involved 690 IVF oocyte donation cycles undergoing PGT-A from multiple clinics across Europe between January 2017 and December 2023. The study population was divided into three groups based on sperm concentration: SO (<5 million sperm/ml), moderate oligozoospermia (MO, 5-16 million sperm/ml), and a normozoospermia control group (≥16 million sperm/ml) for outcome analysis.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The IVF outcomes and variables for couples undergoing oocyte donor cycles were investigated. ICSI was performed in all cycles using fresh sperm samples that were assessed for standard semen parameters with fresh or frozen donated oocytes. All of the resulting embryos were biopsied at the blastocyst stage for PGT-A, and all transfers were of single embryos performed in subsequent cycles after vitrification and warming. Statistical analysis was performed using multivariate regression models to identify correlations between rates of oligozoospermia and clinical, embryological and genetic outcomes.
The study included 690 couples, in the SO (N = 202), MO (N = 102), and the control normozoospermia (N = 386) groups. The SO group had significantly lower sperm motility (P < 0.0001) and significantly reduced fertilization rates compared to the MO and control groups (P < 0.01). However, no statistical difference was observed for the blastocyst formation rate (per fertilized oocyte). Mostly due to the reduced fertilization rates, the number of euploid blastocysts obtained was significantly lower in the SO group (P = 0.007), however, this did not affect the pregnancy, biochemical or clinical miscarriage (P = 0.37, P = 0.22, and P = 0.86), or CLBRs (P = 0.26) after single blastocyst transfers. The multivariate analysis showed no effect of SO or MO on aneuploidy, miscarriage, or live birth rates. Interestingly, the PGT laboratory strategy (<0.001) was associated with the rate of euploid blastocysts but had no significant effect on pregnancy outcomes.
LIMITATIONS, REASONS FOR CAUTION: This is a retrospective observational study focusing on outcomes associated with reduced sperm concentration. Other elements of severe male factor infertility may have different associations with outcomes. Also, potential confounding factors including male lifestyle factors that can influence sperm quality were not considered.
In this oocyte donation setting, we demonstrated that SO is unlikely to significantly affect IVF outcomes following blastocyst development, which contradicts previous findings in less controlled settings. This suggests that male factor infertility in the setting of oocyte donation is not an indication per se to perform PGT-A. These results provide reassurance for couples when undergoing treatment with oocyte donation that any related male factor infertility will not significantly impact treatment outcomes. Further research should use similar controlled oocyte donation settings to investigate other severely impaired sperm parameters to better understand associations with paternal embryonic aneuploidy and IVF outcomes, guiding a more informed path for male factor infertility treatment.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was used and the authors have no conflicting interests.
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男性因素导致的严重精子浓度受损(少精子症)是否会影响体外受精(IVF)供卵周期后的胚胎非整倍体率和临床结果?
在使用供体卵母细胞的IVF周期中,严重少精子症(SO)不会显著影响胚胎整倍体率、IVF结局或累积活产率(CLBRs)。
此前,严重少精子症与精子染色体异常率升高以及胚胎发育率改变和较差的生殖结局有关。然而,在进行胚胎植入前非整倍体基因检测(PGT-A)的供卵周期中,在女性年龄受控的情况下,严重男性因素不育对胚胎非整倍体率和IVF成功率的确切影响仍未完全了解。
研究设计、规模、持续时间:这项回顾性观察队列研究涉及2017年1月至2023年12月期间欧洲多家诊所进行PGT-A的690个IVF供卵周期。根据精子浓度将研究人群分为三组进行结局分析:严重少精子症组(<500万精子/毫升)、中度少精子症组(MO,500-1600万精子/毫升)和正常精子对照组(≥1600万精子/毫升)。
参与者/材料、环境、方法:研究了接受卵母细胞供体周期的夫妇的IVF结局和变量。所有周期均使用新鲜精子样本进行卵胞浆内单精子注射(ICSI),并对新鲜或冷冻捐赠的卵母细胞评估标准精液参数。所有产生的胚胎在囊胚阶段进行活检以进行PGT-A,所有移植均为单胚胎移植,在玻璃化和复温后的后续周期中进行。使用多变量回归模型进行统计分析,以确定少精子症率与临床、胚胎学和遗传学结局之间的相关性。
该研究纳入了690对夫妇,分为严重少精子症组(N = 202)、中度少精子症组(N = 102)和正常精子对照组(N = 386)。与中度少精子症组和对照组相比,严重少精子症组的精子活力显著降低(P < 0.000),受精率显著降低(P < 0.01)。然而,囊胚形成率(每受精卵母细胞)未观察到统计学差异。主要由于受精率降低,严重少精子症组获得的整倍体囊胚数量显著减少(P = 0.007),然而,这并不影响单囊胚移植后的妊娠、生化或临床流产率(P = 0.37、P = 0.22和P = 0.86)或累积活产率(P = 0.26)。多变量分析显示,严重少精子症或中度少精子症对非整倍体率、流产率或活产率无影响。有趣的是,PGT实验室策略(P < 0.001)与整倍体囊胚率相关,但对妊娠结局无显著影响。
局限性、谨慎原因:这是一项回顾性观察研究,重点关注与精子浓度降低相关的结局。严重男性因素不育的其他因素可能与结局有不同的关联。此外,未考虑可能影响精子质量的潜在混杂因素,包括男性生活方式因素。
在这种供卵环境中,我们证明严重少精子症不太可能显著影响囊胚发育后的IVF结局,这与之前在控制较差的环境中的研究结果相矛盾。这表明在供卵情况下,男性因素不育本身并不是进行PGT-A的指征。这些结果为接受供卵治疗的夫妇提供了保证,即任何相关的男性因素不育都不会显著影响治疗结局。进一步的研究应使用类似的受控供卵环境来研究其他严重受损的精子参数,以更好地了解与父源性胚胎非整倍体和IVF结局的关联,为男性因素不育治疗提供更明智的指导。
研究资金/利益冲突:未使用外部资金,作者无利益冲突。
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