Comparative evaluation of metformin & sitaformin in classic PCOS patients undergoing intracytoplasmic sperm injection: A randomized controlled pilot study

Background & objectives: Studies have shown that insulin resistance and hyperinsulinaemia play a major role in the pathogenesis of polycystic ovary syndrome (PCOS). Therefore, the use of insulin sensitizing drugs in the treatment of PCOS has attracted the attention of medicine and researchers. The aim of this study was to investigate the effects of sitaformin (sitagliptin/metformin) and metformin on the quality of oocyte and embryo in classic PCOS patients undergoing intracytoplasmic sperm injection (ICSI). Methods: Sixty patients of PCOS (25-35 yr) were randomly allocated into three groups (n=20, each group): a metformin-treated group (administered metformin 500 mg twice daily), a sitaformin-treated group (administered sitaformin 50/500 mg twice daily) and a placebo group. Participants in all the groups received the drug two months prior to the start of the ovulation cycle and treatment continued until the day of the oocyte aspiration. Results: Serum insulin and total testosterone levels decreaseed significantly after treatment in both the treatment groups as compared to the placebo (P<0.05). A significant decrease in the number of immature oocytes [MI + germinal vesicle (GV) stage] was observed in metformin and sitaformin groups as compared to the placebo. In addition, sitaformin group when compared to the metformin group showed a significant decrease in the number of immature oocytes (P<0.05). The number of mature and normal MII oocytes increased significantly in both the treatment groups compared to the placebo group (P<0.05). The number of mature and normal oocytes increased in sitaformin group in comparison to the metformin group, but the difference was not significant. There was a significant increase in the number of grade I embryos, fertilization and cleavage rates in the sitaformin group compared to the other groups (P<0.05). Interpretation & conclusions: This is the first study to compare the impact of sitaformin with metformin on oocyte and embryo quality in women with PCOS undergoing a gonadotropin-releasing hormone (GnRH) antagonist cycle. In conclusion, sitaformin can be more effective in decreasing immature oocytes and increasing the quality of embryos than the use of metformin.

Effect of Insemination Methods on Pregnancy Outcomes of Day 6 Blastocyst Transfer in Frozen Cycles / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of two different insemination methods， conventional in vitro fertilization （IVF） and intracytoplasmic sperm injection （ICSI）， on pregnancy outcomes in patients with frozen-thawed D6（day 6） blastocyst transfer. MethodsA retrospective cohort study was conducted to analyze the clinical data of patients with thawed D6 blastocyst transfer between January 2018 and April 2020 at the Fertility Center of the Third Hospital of Sun Yat-sen University， divided into conventional IVF group （446 cycles ） and ICSI fertilization group （200 cycles） according to the fertilization method. Patients were divided into those with a history of D5（day 5） blastocyst transfer and those without. The patients’ general characteristics， blastocyst quality， and pregnancy outcomes of the two groups were compared. ResultsBMI， years of infertility， and basal FSH were not statistically significant in the IVF and ICSI groups （P > 0.05）. Regardless of the history of D5 transfer， patients in the ICSI group were younger than those in the IVF group （P < 0.001）， the proportion of primary infertility was significantly higher in the ICSI group （P < 0.001）， and the number of oocytes obtained and the number of normally fertilized oocytes in the ICSI group were higher than those in the conventional IVF fertilization group （P < 0.001）. The proportion of stage V and Ⅵ blastocysts was significantly higher in the conventional IVF group than in the ICSI group （21.6 % vs. 3.14 %， P < 0.001）. High-quality blastocysts with an ICM score of A were significantly higher in the ICSI group than in the IVF group （23.8 % vs. 14.3 %， P = 0.01）. The HCG-positive and clinical pregnancy rates were significantly higher in the ICSI group than in the IVF group （65.5 % vs. 48.4 %， P < 0.001； 56 % vs. 41.3 %， P = 0.001）， and embryo implantation and live birth rates were also higher in the ICSI group than in the conventional IVF group （43.8 % vs. 30.9 %， P < 0.001； 43.0 % vs. 31.8 %， P = 0.006）. After correcting for age and number of oocytes obtained between the two groups， the clinical pregnancy rate was still significantly higher in the ICSI group than in the conventional IVF group （OR： 1.590， 95 % CI： 1.030， 2.455， P = 0.036）. Infant birth weight was lower in the ICSI group than in the IVF group （P = 0.016）， and the differences in preterm birth rate， sex ratio， and mode of delivery were not statistically significant between the two groups. ConclusionsClinical pregnancy and live birth rates after thawing and transfer of D6 blastocysts fertilized by ICSI are higher than those of D6 blastocysts fertilized by conventional IVF， which may be related to the different factors contributing to the slow development of blastocysts in patients who received different fertilization methods. The relatively good pregnancy outcome after the transfer of thawed D6 blastocysts fertilized by ICSI may compensate to some extent for the difference in pregnancy outcome due to the relatively slow blastocyst development and a relatively higher proportion of D6 blastocysts after ICSI fertilization in male infertility patients.

Application of IVF/ICSI-ET in infertility patients with polycystic ovary syndrome combined with insulin resistance / 中华内分泌外科杂志

Objective:To analyze the clinical outcome of vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in infertile patients with polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) .Methods:A total of 257 PCOS infertile patients undergoing IVF/ICSI-ET from Jan. 2018 to Dec. 2020 were included and retrospectively analyzed. The patients were divided into IR group (HOMA-IR≥2.5, 130 cases) and non-IR group (HOMA-IR<2.5, 127 cases) according to the level (median 2.5) of homeostasis model assessment of insulin resistance index (HOMA-IR) . The levels of basic sex hormones [follicular stimulating hormone (FSH) , luteinizing hormone (LH) , estradiol (E2) , testosterone (T) , progestational hormone (P) , anti-mullerian hormone (AMH) ] and numbers of basic sinus follicles, levels of blood glucose and insulin at 30min, 60min and 120min after glucose administration and fasting and proconceptive pregnancy outcome indicators[gonadotropin (Gn) use time and dose, number of eggs obtained, fertilization rate, high-quality embryonic rate, occurrence rate of ovarian hyperstimulation syndrome (OHSS) , implantation rate, clinical pregnancy rate, biochemical pregnancy rate, abortion rate, live birth rate and pregnancy complications] were compared between the two groups. The influencing factors of clinical outcomes were analyzed by Logistic regression.Results:The levels of basic LH [ (8.86±1.60) mIU/ml vs (6.54±1.12) mIU/ml], T[ (63.20±7.47) ng/dl vs (52.11±5.69) ng/dl] in IR group was significantly higher than those in non-IR group ( P<0.05) . At different time-point, the levels of blood glucose and insulin in IR group were significantly higher than those in non-IR group ( P<0.05) . The Gn dose [ (1947.35±129.13) IU vs (1522.70±88.41) IU] and abortion rate [32.69% (17/52) vs 13.70% (10/73) ] in IR group was significantly higher than those in non-IR group ( P<0.05) , and the clinical pregnancy rate [40.00% (52/130) vs 57.48% (73/127) ] and live birth rate [51.92% (27/52) vs 72.60% (53/73) ] was significantly lower than those in non-IR group ( P<0.05) . Logistic regression analysis showed that age, BMI, basic LH, basic T and HOMA-IR was independent risk factors for clinical outcome of IVF/ICSI-ET in infertility patients with PCOS ( P<0.05) , and basic AMH and Gn dose were protective factors for clinical outcome ( P<0.05) . Conclusion:IR negatively affects the clinical outcome of IVF/ICSI-ET in infertile patients with PCOS, HOMA-IR is a risk factor for clinical outcomes, and IR should be evaluated in time for infertile patients with PCOS.

Influence of the sperm DNA fragmentation index on the outcome of rescue ICSI and the clinical value of rescue ICSI / 中南大学学报(医学版)

OBJECTIVES@#As a remedy for the failure of in vitro fertilization (IVF), rescue intracytoplasmic sperm injection (R-ICSI) has been widely carried out, but it has failed to significantly improve the fertilization rate and clinical pregnancy rate. Sperm DNA fragmentation index (DFI) was highly correlated with pregnancy outcome of artificial assisted reproduction. This study aims to investigate the effect of the sperm DFI on the outcome of R-ICSI and the clinical value of R-ICSI.@*METHODS@#This retrospective analysis was conducted among 140 infertile couples receiving R-ICSI in from January 2014 to December 2019. The subjects were assigned into a total fertilization failure (TFF)+low DFI group (R-ICSI after TFF and DFI<30%) (n=63), a TFF+high DFI group (R-ICSI after TFF and DFI≥30%) (n=16), a partial fertilization failure (PFF)+low DFI group (R-ICSI after PFF and DFI<30%) (n=52), a PFF+high DFI group (R-ICSI after PFF and DFI≥30%) (n=9). All transferred embryos were come from R-ICSI. The general clinical data [infertility duration, male age, female age, basal serum level of follicle stimulating hormone (FSH), basal serum level of luteinizing hormone (LH), antral follicle count, endometrial thickness of human chorionic gonadotropin (HCG) day, and eggs] and R-ICSI cycle outcomes (fertilization rate, normal fertilization rate, cleavage rate, good embryo rate, implantation rate, clinical pregnancy rate and live birth rate) were analyzed. In addition, the effect of R-ICSI on the fertilization outcome of conventional IVF total fertilization failure and partial fertilization failure was explored.@*RESULTS@#There was no significant difference in the general clinical data and R-ICSI cycle outcome between the TFF+low DFI group and the TFF+high DFI group (all P>0.05). There was no significant difference in the general clinical data between the PFF+low DFI group and the PFF+high DFI group (all P>0.05). The fertilization rate and normal fertilization rate in the PFF+low DFI group were significantly higher than those in the PFF+high DFI group (85.40% vs 72.41%, 71.90% vs 58.62%, respectively; both P<0.05). However, there was no significant difference in cleavage rate, good embryo rate, implantation rate, clinical pregnancy rate, and live birth rate between the 2 groups (all P>0.05). The R-ICSI cycle of TFF: A total of 79 fresh cycles, 57 fresh transplant cycles, a total of 761 unfertilized oocytes, and 584 M II oocytes were treated with R-ICSI, the fertilization rate was 83.22%, the normal fertilization rate was 75.51%, the cleavage rate was 98.15%, the good embryo rate was 40.74%, the implantation rate was 30.56%, and the clinical pregnancy rate was 43.86%; 29 live births were obtained. The R-ICSI cycle of PFF: A total of 61 fresh cycles, 31 fresh transplant cycles, a total of 721 unfertilized oocytes, and 546 M II oocytes were treated with R-ICSI; the fertilization rate was 83.33%, the normal fertilization rate was 69.78%, the cleavage rate was 97.36%, the good embryo rate was 44.39%, the implantation rate was 25.42%, and the clinical pregnancy rate was 45.16%; 12 live births were obtained.@*CONCLUSIONS@#In the case of partial fertilization failure of IVF, the sperm DFI affects the fertilization rate and normal fertilization rate of R-ICSI; whether it is a TFF of IVF or PFF of IVF, ICSI can be used as an effective remedy way.

Comparison of intracytoplasmic sperm injection (ICSI) outcomes in infertile men with spermatogenic impairment of differing severity / 亚洲男科学杂志(英文版)

The extent of spermatogenic impairment on intracytoplasmic sperm injection (ICSI) outcomes and the risk of major birth defects have been little assessed. In this study, we evaluated the relationship between various spermatogenic conditions, sperm origin on ICSI outcomes, and major birth defects. A total of 934 infertile men attending the Center for Reproductive Medicine of Ren Ji Hospital (Shanghai, China) were classified into six groups: nonobstructive azoospermia (NOA; n = 84), extremely severe oligozoospermia (esOZ; n = 163), severe oligozoospermia (sOZ, n = 174), mild oligozoospermia (mOZ; n = 148), obstructive azoospermia (OAZ; n = 155), and normozoospermia (NZ; n = 210). Rates of fertilization, embryo cleavage, high-quality embryos, implantation, biochemical and clinical pregnancies, abortion, delivery, newborns, as well as major birth malformations, and other newborn outcomes were analyzed and compared among groups. The NOA group showed a statistically lower fertilization rate (68.2% vs esOZ 77.3%, sOZ 78.0%, mOZ 73.8%, OAZ 76.6%, and NZ 79.3%, all P < 0.05), but a significantly higher implantation rate (37.8%) than the groups esOZ (30.1%), sOZ (30.4%), mOZ (32.6%), and OAZ (31.0%) (all P < 0.05), which was similar to that of Group NZ (38.4%). However, there were no statistically significant differences in rates of embryo cleavage, high-quality embryos, biochemical and clinical pregnancies, abortions, deliveries, major birth malformations, and other newborn outcomes in the six groups. The results showed that NOA only negatively affects some embryological outcomes such as fertilization rate. There was no evidence of differences in other embryological and clinical outcomes with respect to sperm source or spermatogenic status. Spermatogenic failure and sperm origins do not impinge on the clinical outcomes in ICSI treatment.

Severe male factor in in vitro fertilization: definition, prevalence, and treatment. An update / 亚洲男科学杂志(英文版)

Infertility affects 10%-15% of couples worldwide. Of all infertility cases, 20%-70% are due to male factors. In the past, men with severe male factor (SMF) were considered sterile. Nevertheless, the development of intracytoplasmic sperm injection (ICSI) drastically modified this scenario. The advances in assisted reproductive technology (ART), specifically regarding surgical sperm retrieval procedures, allowed the efficacious treatment of these conditions. Yet, before undergoing ICSI, male factor infertility requires careful evaluation of clinical and lifestyle behavior together with medical treatment. Epidemiologically speaking, women whose male partner is azoospermic tend to be younger and with a better ovarian reserve. These couples, in fact, are proposed ART earlier in their life, and for this reason, their ovarian response after stimulation is generally good. Furthermore, in younger couples, azoospermia can be partially compensated by the efficient ovarian response, resulting in an acceptable fertility rate following in vitro fertilization (IVF) techniques. Conversely, when azoospermia is associated with a reduced ovarian reserve and/or advanced maternal age, the treatment becomes more challenging, with a consequent reduction in IVF outcomes. Nonetheless, azoospermia seems to impair neither the euploidy rate at the blastocyst stage nor the implantation of euploid blastocysts. Based on the current knowledge, the assessment of male infertility factors should involve: (1) evaluation - to diagnose and quantify seminologic alterations; (2) potentiality - to determine the real possibilities to improve sperm parameters and/or retrieve spermatozoa; (3) time - to consider the available "treatment window", based on maternal age and ovarian reserve. This review represents an update of the definition, prevalence, causes, and treatment of SMF in a modern ART clinic.

Modified strict sperm morphology threshold aids in the clinical selection of conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) / 亚洲男科学杂志(英文版)

For infertility treatment, the selection of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is decided by multiplying indicators (including fallopian tube factors, semen count, and semen motility), except for sperm morphology. In this study, we conducted a retrospective analysis, from implantation to birth, over a period of 5 years. A total of 1873 couples with primary or secondary fallopian tube factors and an increased defective sperm morphology rate (DSMR) were divided into different groups to receive IVF or ICSI cycles. By comparing the outcomes, we found that the F1 group (DSMR <96%, IVF group 1) had higher cleavage rate, biochemical pregnancy rate, clinical pregnancy rate, and live birth rate than the F3 group (DSMR >98%, IVF group 3; P < 0.05). In contrast, there was no significant difference in the ICSI subgroups. Furthermore, a comparison of the outcomes between IVF and ICSI showed that the S3 group (DSMR >98%, ICSI group 3) had higher cleavage rate (P < 0.001), biochemical pregnancy rate (P < 0.05), clinical pregnancy rate (P < 0.05) and live birth rate (P < 0.05) than the F3 group. However, the ICSI subgroup had a lower two pronuclei fertilization rate than the IVF subgroup (P < 0.05). Our data suggest that the sperm morphology should also be considered when selecting IVF or ICSI combined with other semen parameters before the first assisted reproductive technologies (ART) cycle, especially for males with severe sperm defects.

Random sperm DNA fragmentation index is not associated with clinical outcomes in day-3 frozen embryo transfer / 亚洲男科学杂志(英文版)

Damage to sperm DNA was proposed to play an important role in embryonic development. Previous studies focused on outcomes after fresh embryo transfer, whereas this study investigated the influence of sperm DNA fragmentation index (DFI) on laboratory and clinical outcomes after frozen embryo transfer (FET). This retrospective study examined 381 couples using cleavage-stage FET. Sperm used for intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF) underwent density gradient centrifugation and swim up processing. Sperm DFI had a negative correlation with sperm motility (r = -0.640, P < 0.01), sperm concentration (r = -0.289, P < 0.01), and fertilization rate of IVF cycles (r = -0.247, P < 0.01). Sperm DFI examined before and after density gradient centrifugation/swim up processing was markedly decreased after processing (17.1% vs 2.4%, P < 0.01; 65 randomly picked couples). Sperm progressive motility was significantly reduced in high DFI group compared with low DFI group for both IVF and ICSI (IVF: 46.9% ± 12.4% vs 38.5% ± 12.6%, respectively; ICSI: 37.6% ± 14.1% vs 22.3% ± 17.8%, respectively; both P < 0.01). The fertilization rate was significantly lower in high ( ≥25%) DFI group compared with low (<25%) DFI group using IVF (73.3% ± 23.9% vs 53.2% ± 33.6%, respectively; P < 0.01) but was equivalent in high and low DFI groups using ICSI. Embryonic development and clinical outcomes after FET were equivalent for low and high DFI groups using ICSI or IVF. In this study, sperm DFI did not provide sufficient information regarding embryo development or clinical outcomes for infertile couples using FET.

The effect of timing of oocyte denudation from oocyte retrieval in the total fertilization failure among in vitro fertilization - Intracytoplasmic sperm injection cycles

@#<p>Objective: This study aimed to evaluate the effect of oocyte incubation after retrieval in TFF among IVF-ICSI and identify factors affecting total fertilization failure (TFF).</p><p>Methods: This is a retrospective cohort study, involving 995 IVF cycles using the antagonist protocol that were clustered into three timings of oocyte denudation from retrieval : Group 1: <1 hour, Group 2: ?1 hour to <2hours and Group 3: ?2hours. Other variables considered were etiology of infertility, female age, days of stimulation and total number of oocytes retrieved.</p><p>Results: Overall TFF was 4.5%. TFF among groups were 4.8%, 5.8% and 3.2%, respectively. Multiple logistic regression analysis showed that oocyte incubation prior to denudation for ? 2 hours tend to decrease TFF incidence. Among factors studied, male factor infertility and a low number of oocytes adversely affect TFF.</p><p>Conclusion: Timing of incubation of oocyte did not significantly affect the occurrence of TFF. Among factors studied, male factor infertility and a low number of oocytes adversely affect TFF.</p>

Effect of dyslipidemia on clinical outcome of infertility patients receiving donor eggs / 中华妇产科杂志

Objective:To explore the effect of dyslipidemia on the clinical outcome of intracytoplasmic sperm injection-embryo transfer (ICSI-ET) in infertility patients receiving donor eggs.Methods:A total of 118 patients were selected to receive egg donors and ICSI-ET at the First Affiliated Hospital of Nanjing Medical University between April 2007 and December 2020. According to the levels of triacylglycerol, serum cholesterol, high density lipoprotein (HDL), and low density lipoprotein, they were divided into dyslipidemia group (35 cases) and normal blood lipids group (83 cases). The influence of body mass index (BMI) and age was adjusted by 1∶1 propensity score matching, and the general condition and clinical outcome of the two groups were analyzed retrospectively. Finally, the relationship between lipid composition and clinical outcome was analyzed according to patients′ age and BMI.Results:(1) Comparing the pre-matching dyslipidemia group with the normal blood lipids group, the BMI of the dyslipidemia group was significantly higher than that of the normal blood lipids group [(23.5±2.4) vs (22.4±2.7) kg/m 2], and the embryo implantation rate was significantly lower than that of the normal blood lipids group [13.6% (8/59) vs 27.3% (36/132)], the differences were statistically significant (both P<0.05). (2) There were no significant differences in years of infertility, number of pregnancies, number of abortions, number of transplanted embryos, protocol of endometrial preparation, endometrial thickness on transplantation day and high quality embryo rate between the two groups, through propensity score matching (all P>0.05). The biochemical pregnancy rate [28.6% (10/35)], embryo implantation rate [13.6% (8/59)] and live birth rate [20.0% (7/35)] in dyslipidemia group were significantly lower than those in the normal blood lipids group ( P<0.05). The clinical pregnancy rate was lower than that of the normal blood lipids group ( P>0.05). (3) The results of stratified analysis showed that the level of HDL in the clinically non-pregnant group was significantly lower than that in the pregnant group in patients ≤ 35 years old [(1.5±0.3) vs (1.8±0.5) mmol/L; P<0.05]. In the overweight recipient patients, the level of HDL of the clinically non-pregnant group was lower than that of the pregnant group ( P>0.05). Conclusions:Dyslipidemia significantly reduces the biochemical pregnancy rate, embryo implantation rate and live birth rate in patients with receiving donor eggs. Especially in patients aged ≤35 years old, the reduction of HDL is closely related to adverse pregnancy outcomes.

Improving Implantation Rate in 2nd ICSI Cycle through Ovarian Stimulation with FSH and LH in GNRH Antagonist Regimen / Melhorando a taxa de implantação no 2° ciclo de ICSI através do estímulo ovariano com FSH e LH no regime com antagonista do GnRH

Abstract Objective To investigate whether patients with a previous recombinant follicle stimulating hormone (rFSH)-stimulated cycle would have improved outcomes with rFSH + recombinant luteinizing hormone (rLH) stimulation in the following cycle. Methods For the present retrospective case-control study, 228 cycles performed in 114 patients undergoing intracytoplasmic sperm injection (ICSI) between 2015 and 2018 in an in vitro fertilization (IVF) center were evaluated. Controlled ovarian stimulation (COS) was achieved with rFSH (Gonal-f, Serono, Geneva, Switzerland) in the first ICSI cycle (rFSH group), and with rFSH and rLH (Pergoveris, Merck Serono S.p.A, Bari, Italy) in the second cycle (rFSH + rLH group). The ICSI outcomes were compared among the groups. Results Higher estradiol levels, oocyte yield, day-3 high-quality embryos rate and implantation rate, and a lower miscarriage rate were observed in the rFSH + rLH group compared with the rFSH group. In patients < 35 years old, the implantation rate was higher in the rFSH + rLH group compared with the rFSH group. In patients ≥ 35 years old, higher estradiol levels, oocyte yield, day-3 high-quality embryos rate, and implantation rate were observed in the rFSH + rLH group. In patients with ≤ 4 retrieved oocytes, oocyte yield, mature oocytes rate, normal cleavage speed, implantation rate, and miscarriage rate were improved in the rFSH + rLH group. In patients with ≥ 5 retrieved oocytes, higher estradiol levels, oocyte yield, and implantation rate were observed in the rFSH + rLH group. Conclusion Ovarian stimulation with luteinizing hormone (LH) supplementation results in higher implantation rates, independent of maternal age and response to COS when compared with previous cycles stimulated with rFSH only. Improvements were also observed for ICSI outcomes and miscarriage after stratification by age and retrieved oocytes.

Resumo Objetivo: Investigar se há algum efeito da suplementação com hormônio luteinizante (LH, na sigla em inglês) no regime com antagonista do hormônio liberador de gonadotropina (GnRH, na sigla em inglês) sobre os resultados dos ciclos consecutivos de injeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês). Métodos Para o presente estudo retrospectivo de caso-controle, foram avaliados 228 ciclos de microinjeção intracitoplasmática de espermatozoides (ICSI, na sigla em inglês) realizados em 114 pacientes entre 2015 e 2018 em um centro privado de fertilização in vitro (FIV) afiliado a uma universidade. O estímulo ovariano controlado (EOC) foi feito com hormônio folículo- estimulante recombinante (rFSH, na sigla em inglês) (Gonal-f, Serono, Genebra, Suíça) no primeiro ciclo de ICSI (grupo rFSH), e com rFSH e rLH (Pergoveris, Merck Serono S.p.A, Bari, Itália) no segundo ciclo (grupo rFSH + rLH). Os desfechos dos ciclos de ICSI foram comparados entre os grupos. Resultados Níveis mais elevados de estradiol, de recuperação oocitária, taxa de embriões de alta qualidade no 3° dia e taxa de implantação, e menor taxa de aborto foram observados no grupo rFSH + rLH. Em pacientes < 35 anos, a taxa de implantação foi maior no grupo rFSH + rLH em comparação com o grupo rFSH. Em pacientes com ≥ 35 anos, maiores níveis de estradiol, recuperação oocitária, a taxa de embriões de alta qualidade no 3° dia e a taxa de implantação foram observados no grupo rFSH + rLH. Em pacientes com baixa resposta ao EOC (≤ 4 oócitos recuperados), a recuperação oocitária, a taxa de oócitos maduros, a taxa de velocidade normal de clivagem, a taxa de implantação e a taxa de aborto foram melhoradas no grupo rFSH + rLH. Em pacientes com resposta normal ao EOC (≥ 5 oócitos recuperados), níveis mais elevados de estradiol, recuperação oocitária e taxa de implantação foram observados no grupo rFSH + rLH. Conclusão A estimulação ovariana com suplementação de LH resultou em taxas de implantação mais altas, independentemente da idade materna e da resposta ao EOC, em comparação com os ciclos anteriores estimulados apenas com rFSH. Melhorias também foram observadas nos resultados da ICSI e na taxa de aborto quando as pacientes foram estratificadas por idade e número de oócitos recuperados.

Influence of sperm morphology on pregnancy outcome and offspring in / 亚洲男科学杂志(英文版)

Sperm morphology was once believed as one of the most predictive indicators of pregnancy outcome in assisted reproductive technology (ART). However, the impact of teratozoospermia on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes and its offspring remains inconclusive. In order to evaluate the influence of teratozoospermia on pregnancy outcome and newborn status after IVF and ICSI, a retrospective study was conducted. This was a matched case-control study that included 2202 IVF cycles and 2574 ICSI cycles and was conducted at the Reproductive and Genetic Hospital of CITIC-Xiangya in Changsha, China, from June 2013 to June 2018. Patients were divided into two groups based on sperm morphology: teratozoospermia and normal sperm group. The pregnancy outcome and newborn outcome were analyzed. The results indicated that couples with teratozoospermia had a significantly lower optimal embryo rate compared to those with normal sperm morphology in IVF (P = 0.007), while there were no statistically significant differences between the two groups in terms of the fertilization rate, cleavage rate, implantation rate, and pregnancy rate (all P > 0.05). Additionally, teratozoospermia was associated with lower infant birth weight in multiple births after IVF. With regard to ICSI, there was no significant difference in both pregnancy outcome and newborn outcome between the teratozoospermia and normal groups (both P > 0.05). Furthermore, no increase in the risk of birth defects occurred in the teratozoospermia group after IVF/ICSI. Consequently, we believe that teratozoospermia has limited predictive value for pregnancy outcomes in IVF/ICSI, and has little impact on the resulting offspring if multiple pregnancy is avoided.

Abnormal fertilization in ICSI and its association with abnormal semen parameters: a retrospective observational study on 1855 cases / 亚洲男科学杂志(英文版)

Intracytoplasmic sperm injection (ICSI) efficiently addresses male factor infertility. However, the occurrence of abnormal fertilization, mainly characterized by abnormal pronuclei (PN) patterns, merits investigation. To investigate abnormal fertilization patterns following ICSI and identify their respective associations with abnormal parameters in semen analysis (SA), a retrospective observational study including 1855 cycles was performed. Male infertility diagnosis relied on the 2010 WHO criteria. The population was divided into groups based on their SA results. The presence of 2PNs and extrusion of the second polar body (PB) indicated normal fertilization. A Kruskal-Wallis test along with a Wilcoxon post hoc evaluation and Bonferroni correction was employed for comparison among the groups. For the pregnancy rate, logistic regression was employed. No correlation was established between the SA abnormalities and the 1PN or 3PN formation rates. The highest and lowest 0PN rates were reported for the oligoasthenoteratozoospermic and normal groups, respectively. The lowest cleavage formation rates were identified in the oligoasthenozoospermic and oligoasthenoteratozoospermic groups. The aforementioned groups along with the oligoteratozoospermic group similarly presented the lowest blastocyst formation rates. For the clinical pregnancy rate, no statistically significant difference was observed. In conclusion, the incidence of two or more abnormal SA parameters - with the common denominator being oligozoospermia - may jeopardize normal fertilization, cleavage, and blastocyst rates. Once the developmental milestone of achieving blastocyst stage status was achieved, only oligoasthenozoospermia and oligoasthenoteratozoospermia were associated with lower rates. Interestingly, following adjustment for the number of blastocysts, no statistically significant differences were observed.

A novel homozygous frameshift mutation in / 亚洲男科学杂志(英文版)

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

Sperm retrieval and intracytoplasmic sperm injection outcomes in men with cystic fibrosis disease versus congenital bilateral absence of the vas deferens / 亚洲男科学杂志(英文版)

Recent data suggest that cystic fibrosis transmembrane conductance regulator (CFTR) gene alterations negatively impact male fertility beyond obstruction. We sought to compare gene alterations, sperm retrieval rates, and intracytoplasmic sperm injection (ICSI) outcomes among men with cystic fibrosis (CF) disease and congenital bilateral absence of the vas deferens (CBAVD) only. We retrospectively evaluated all men who underwent surgical sperm retrieval at two academic, high-volume andrology centers from 2010 to 2018. Only men with documented CFTR alterations and obstructive azoospermia from either CBAVD or CF were included. Differences between groups for CFTR abnormality, sperm retrieval, and ICSI outcomes were statistically analyzed. Overall, 39 patients were included with 10 in the CF and 29 in the CBAVD groups. Surgical sperm retrieval rates were significantly lower in the CF group for sperm concentration (14.8 × 10

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia / 亚洲男科学杂志(英文版)

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

The hamster egg penetration test may decrease intracytoplasmic sperm injection utilization while maintaining high conventional fertilization rates / 亚洲男科学杂志(英文版)

This was a cohort study of in vitro fertilization (IVF) subjects at the University of Utah, Salt Lake City (UT, USA) utilizing partner sperm. Cycles where both the hamster egg penetration test (HEPT) and semen analysis were performed within 2 years prior to IVF cycles were stratified into four groups based on a normal or an abnormal HEPT and morphology. The mean conventional and intracytoplasmic sperm injection (ICSI) fertilization rates were calculated in each group. We performed a univariate analysis on the primary outcome comparing clinically interesting subjects. We performed a cost-effectiveness analysis of a policy of HEPT versus universal ICSI in couples with an abnormal morphology. Among patients with a normal HEPT, there was no difference in the mean conventional fertilization rates between those with a normal and an abnormal morphology. There was no difference in the mean conventional fertilization rates between subjects with a normal morphology without a hamster test and those with a normal HEPT without a morphology assessment. In 1000 simulated cycles with an abnormal morphology, a policy of HEPT was cost saving compared to universal ICSI, yet produced similar fertilization rates. The HEPT is similar to the World Health Organization edition 5 (WHO-5) morphology in predicting successful conventional fertilization while allowing decreased utilization of ICSI. A policy of HEPT for males with abnormal morphology saves cost in selecting couples for a fertilization method.

Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection / 亚洲男科学杂志(英文版)

The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.

Impact of BMI on fresh cycle embryo transfer outcome of IVF/ICSI in patients with early follicular phase prolonged protocol / 中华妇产科杂志

Objective:To investigate the impact of body mass index (BMI) on clinical effect and fresh cycle embryo transfer pregnancy outcome of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) in patients with early follicular phase prolonged protocol.Methods:From January 1st, 2018 to July 1st, 2020, 2 257 cases of early follicular long-term protocol in IVF/ICSI and embryo transfer were collected using the clinical assisted reproductive technologies management system software database of the First Affiliated Hospital of Nanjing Medical University. Patients were divided into three groups according to the recommended Asian BMI cut-off points: low body mass group (BMI<18.5 kg/m 2), normal body mass group (18.5≤BMI<24.0 kg/m 2), and high body mass group (BMI≥24.0 kg/m 2). The ovarian stimulation characteristics among the groups were investigated. Then 1 741 fresh embryo transfer cycles were selected and divided into three groups as above, and then the ovulation induction and clinical outcomes were analyzed among the groups. Results:There were significant differences in the starting dosage of gonadotrophin (Gn), total dosage of Gn and days of Gn used among the low body mass group, normal body mass group, and high body mass group in the 2 257 IVF/ICSI cycles (all P<0.01). The high body mass group needed the most amount of Gn [(2 159±668) U] and longest Gn days [(12.3±2.5) days]. The estradiol and progesterone levels [(7 474±4 852) pmol/L, (3.4±1.9) nmol/L] on hCG trigger day in the high body mass group were lower than those in the low body mass group and normal body mass group (all P<0.01). The oocytes retrieved in high body mass group (8.4±4.1) were significantly lower than normal body mass group ( P<0.05). The normal fertilization number, the available embryo number and high quality embryo number were all lower in the high body mass group than other two groups, while no significant difference showed (all P>0.05). In 1 741 cycles of fresh embryo transfer, the average number of transplanted embryos in the low body mass group (1.2±0.4) was decreased compared with the other two groups ( P<0.05), while the biochemical pregnancy rate, clinical pregnancy rate and live birth rate in the normal body mass group were higher compared with the other two groups, but the differences showed no statistically significance (all P>0.05). Conclusions:Increased BMI might affect ovulation induction response in early follicular phase prolonged protocol IVF/ICSI patients, leading to the increase of Gn dosage and the extension of Gn induction days. Although there is no significant difference in pregnancy outcome among different BMI groups, considering the increased risk of adverse perinatal outcomes during subsequent pregnancy in overweight or obese patients, certain attention should still be paid to the control of BMI in patients receiving assisted reproduction treatment with early follicular phase prolonged protocol.

Utility of prophylactic cervical cerclage in intra-cytoplasmic sperm injection twins: a prospective study

Background: Several interventions have been used to reduce the rate of preterm birth and prolonging gestation in a twin pregnancy and routine usage of cervical cerclage in twin pregnancy conceived after intra-cytoplasmic sperm injection (ICSI) procedure has found to be beneficial.Methods: Prospective case series studies, series of expectant mothers with twin pregnancy conceived by ICSI were studied under tertiary care hospital setting. A total of 108 cases with twin pregnancy were included during a period of 2016 to 2019. Obstetric profile of all the cases was taken; cervical cerclage procedure was done at 14-16 weeks of gestation (McDonald method) after a normal nuchal translucency scan and a double marker test. Pregnancy outcome parameters like abortion, preterm labour/delivery, premature rupture of membranes (PROM), and mode of delivery, gestational age at delivery, birth weight and neonatal complications were assessed.Results: Mean age of the mothers was 30.61±4.45 years, rates of the pregnancy outcome parameters were abortion 0%, preterm labour 11.1%, premature rupture of membranes (PROM) 9.3%, mean gestational age at delivery was at 34.56±1.71 weeks. Neonatal outcome parameters were mean birth weight was at 2279±470 grams, 77.8% of the neonates had normal APGAR scores. The rates of NICU admission was 28%, RDS– 24.1%, 3.7% had sepsis and 92.6% of neonates survived and 7.4% died.Conclusions: In ICSI twin pregnancies with normal cervical measurements, prophylactic cervical cerclage is effective in prolonging pregnancy and preventing preterm delivery and thereby minimizing neonatal morbidity and mortality.