Genetic causes of macrozoospermia and proposal for an optimized genetic diagnosis strategy based on sperm parameters

Macrozoospermia,characterized by the presence of largeheaded spermatozoa usually carrying several flagella,is one of the most severe phenotypes of male infertility.As in most cases,the gametes are chromosomally abnormal and cannot be used for assisted reproductive technologies(ART)(Ray et al.,2017).In 2007,subjects from consanguineous families were shown to carry the same homozygous deleterious AURKC variant(NM_001015878.2:c.144delC,later renamed c.145delC,p.Leu49TrpfsTer23),establishing AURKC as the first and main gene associated with macrozoospermia(Dieterich et al.,2007).Using flow cytometry,all spermatozoa from patients homozygous for the c.145delC variant were shown to be tetraploid,highlighting a cytokinesis blockage of the first meiotic divisions thus confirming that ART cannot be successful for these patients(Dieterich et al.,2009).

Bilateral versus unilateral cryptorchidism in nonobstructive azoospermia:testicular sperm extraction outcomes

Cryptorchidism is one of the most frequent causes of nonobstructive azoospermia(NOA)in adulthood.Although it is well known that spermatogenesis is more impaired in bilateral than in unilateral cryptorchidism,previous studies have only described small cohorts or inhomogeneous population.Consequently,we analyzed a cohort of 225 men with only a history of cryptorchidism as sole etiopathogenetic factor for NOA,and compared testicular sperm extraction(TESE)outcomes between men with bilateral versus unilateral cryptorchidism.Our results show no difference in follicle-stimulating hormone(FSH)levels and testicular volumes between men with a history of bilateral cryptorchidism compared to unilateral cryptorchidism(median:21.3 IU I^-1 vs 19.3 IU I^-1,P=0.306;and 7.2 ml vs 7.9 ml,P=0.543,respectively).In addition,sperm retrieval rates were similar(66.2%vs 60.0%,P=0.353).Using multivariate analysis,we have found that only a low inhibin B level(above the assay's detection limit)was positively associated with successful sperm retrieval(P<0.05).Regarding intracytoplasmic sperm injection outcomes,we found that cumulative pregnancy rate and live birth rate per cycle were not statistically different between the two groups(17.4%vs 27.8%,P=0.070;and 16.1%vs 26.4%,P=0.067,respectively).Unexpectedly,there was no significant difference in hormonal profiles(FSH,luteinizing hormone[LH],testosterone,and inhibin B levels)and TESE outcomes between unilateral versus bilateral cryptorchidism.This suggests that a history of unilateral cryptorchidism could reflect a bilateral testicular impairment.Interestingly,inhibin B level might be a predictor of successful TESE.

Intrauterine insemination with donor sperm:only the number of motile spermatozoa inseminated influences both pregnancy and live-birth rates

Intrauterine insemination with donor sperm(IUI-D)is an assisted reproductive technology(ART)offered to couples with definitive male infertility or risk of genetic disease transmission.Here,we sought to evaluate our practice in IUI-D and identify factors that influenced the success rate.We performed a retrospective,single-center study of all IUI-D procedures performed at Lille University Medical Center(Lille,France)between January 1,2007,and December 31,2017.Single and multivariate analyses with a mixed logistic model were used to identify factors associated with clinical pregnancies and live births.We included 322 couples and 1179 IUI-D procedures.The clinical pregnancy rate was 23.5%,and the live birth rate was 18.9%per IUI-D.In a multivariate analysis,the women’s age was negatively associated with the live birth rate.The number of motile spermatozoa inseminated was the only factor associated with both clinical pregnancies and live births,with a chosen threshold of 0.75 million.The clinical pregnancy and live birth rates were,respectively,17.3%and 13.0%below the number of motile spermatozoa inseminated threshold and 25.9%and 21.0%at or above the threshold(all P=0.005).The number of motile spermatozoa inseminated was the only factor that significantly influenced both pregnancies and live-birth rates after IUI-D.Indeed,below a threshold of 0.75 million motile spermatozoa inseminated,those rates were significantly lower.Application of this number of motile spermatozoa inseminated threshold may help centers to allocate donations more effectively while maintaining reasonable waiting times for patients.