Impact of vaccination against COVID-19 on the outcomes of in vitro fertilization-embryo transfer: a retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization-embryo transfer (IVF-ET) or not. In this study, we compared the outcome of IVF-ET and the development of follicles and embryos between vaccinated and unvaccinated groups.@*METHODS@#A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software ( http://www.R-project.org/ ) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio.@*RESULTS@#The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) ( P  = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely ( P  = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) ( P  = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) ( P  = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes.@*CONCLUSIONS@#In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines show significant effects.

One Plus One is Better than Two: An Approach Towards a Single Blastocyst Transfer Policy for All IVF Patients / Um mais um é melhor que dois: Uma abordagem pela prática da transferência de embrião único para todos os pacientes de FIV

Abstract Objective It is known that the single embryo transfer (SET) is the best choice to reduce multiples and associated risks. The practice of cryopreserving all embryos for posterior transfer has been increasingly performed for in vitro fertilization (IVF) patients at the risk of ovarian hyperstimulation syndrome or preimplantation genetic testing for aneuploidy. However, its widespread practice is still controverse. The aim of this study was to evaluate how effective is the transfer of two sequential SET procedures compared with a double embryo transfer (DET) in freeze-only cycles. Methods This retrospective study reviewed 5,156 IVF cycles performed between 2011 and 2019, and 506 cycles using own oocytes and freeze-only policy with subsequent elective frozen-thawed embryo transfers (eFET) were selected for this study. Cycles having elective SET (eSET, n = 209) comprised our study group and as control group we included cycles performed with elective DET (eDET, n = 291). In the eSET group, 57 couples who had failed in the 1st eSET had a 2nd eFET, and the estimated cumulative ongoing pregnancy rate was calculated and compared with eDET. Results After the 1st eFET, the ongoing pregnancy rates were similar between groups (eSET: 35.4% versus eDET: 38.5%; p =0.497), but the estimated cumulative ongoing pregnancy rate after a 2nd eFET in the eSET group (eSET + SET) was significantly higher (48.8%) than in the eDET group (p < 0.001). Additionally, the eSET +SET group had a 2.7% rate of multiple gestations, which is significantly lower than the eDET group, with a 30.4% rate (p < 0.001). Conclusion Our study showed the association of freeze-only strategy with until up to two consecutive frozen-thawed eSETs resulted in higher success rates than a frozenthawed DET, while drastically reducing the rate of multiple pregnancies.

Resumo Objetivo Sabe-se que a transferência de embrião único (SET) é a melhor escolha para reduzir as gestações múltiplas e riscos associados. A prática da criopreservação de todos os embriões para transferência posterior tem sido cada vez mais utilizada para fertilização in vitro (FIV), em especial quando há risco de síndrome de hiperestimulação ovariana ou realização de teste genético pré-implantacional. Entretanto, sua utilização disseminada ainda é controversa. O objetivo deste estudo foi avaliar a eficácia de duas SET sequenciais em comparação com uma transferência de embrião dupla (DET) em ciclos de FIV onde todos os embriões foram criopreservados. Métodos Neste estudo retrospectivo foram revisados 5.156 ciclos de FIV realizados entre 2011 e 2019, e 506 ciclos usando oócitos próprios e criopreservação de todos os embriões com transferências eletivas subsequentes de embriões descongelados, foram selecionados para este estudo. Ciclos com transferência eletiva de embrião único (eSET, n = 209) compuseram nosso grupo de estudo e como grupo de controle incluímos os ciclos com transferência eletiva de dois embriões (eDET, n = 291). No grupo eSET, 57 casais que falharam na 1ª tentativa de eSET tiveram uma 2ª eFET e a taxa de gravidez em curso cumulativa foi estimada para o grupo eSET e comparada com o grupo eDET. Resultados Após a 1ª eFET, as taxas de gravidez em curso foram semelhantes entre os grupos (eSET: 35,4% versus eDET: 38,5%; p = 0,497), mas a taxa de gravidez em curso cumulativa estimada após a 2ª eFET no grupo eSET (eSET + SET) foi significativamente maior (48,8%) do que no grupo eDET (p <0,001). Além disso, as taxas de gestação múltipla foram expressivamente inferiores no grupo eSET + SET (2,7%) quando comparado ao grupo eDET (30,4%; p < 0,001). Conclusão Nosso estudo mostrou que a associação das estratégias de congelamento de todos os embriões com até duas eSETs sequenciais resultou em maiores taxas de sucesso do que uma DET com embriões descongelados, além de reduzir drasticamente a ocorrência de gestações múltiplas.

Evaluación de la terapia de reproducción médicamente asistida en 9 años: estudio de cohorte retrospectivo / Medically assisted reproductive therapy assessment in 9 years: retrospective cohort study

OBJETIVO: Describir las tasas de recién nacidos vivos (RNV) y embarazo de la terapia de reproducción médicamente asistida de baja complejidad del Centro de Reproducción Humana de la Universidad de Valparaíso, Chile. MÉTODO: Estudio retrospectivo de todos los ciclos de estimulación ovárica controlada con inseminación intrauterina (IIU) completados, entre los años 2011 y 2019. Se evaluaron las características clínicas basales y los resultados en IIU homólogas y heterólogas según el ciclo inseminado, la causa de infertilidad, el rango etario y el índice de masa corporal (IMC). El desenlace principal fue la tasa de RNV por ciclo inseminado. RESULTADOS: Se estudiaron 1415 ciclos en 700 parejas. La tasa acumulativa de RNV fue del 19,6%, un 18,3% en IIU homóloga y un 39,0% en IIU heteróloga. La tasa de RNV fue del 10,0% al primer ciclo, del 5,8% al segundo ciclo y del 3,7% al tercer o más ciclos. Al separar por IIU heteróloga, esta aumenta al 24,4% al primer ciclo y al 14,6% al segundo ciclo. La tasa de RNV es significativamente mejor en pacientes menores de 35 años (23,7%) y con IMC < 29 (20,8%). CONCLUSIONES: El tratamiento de baja complejidad en pacientes infértiles es una opción terapéutica vigente con una aceptable tasa de RNV por ciclo inseminado. Los resultados están influenciados por la edad y por el IMC.

OBJECTIVE: To describe the rates of live newborns (LNB) and pregnancy of the low complexity therapy of the Centre for Human Reproduction of Universidad de Valparaíso, Chile. METHOD: Retrospective study of all cycles of controlled ovarian stimulation with intrauterine insemination (IUI) completed between 2011-2019. The baseline clinical characteristics and results in homologous and heterologous IUI were evaluated according to inseminated cycle, cause of infertility, age range and body mass index (BMI). The main outcome was rate of LNB per inseminated cycle. RESULTS: 1415 cycles were studied in 700 couples. The cumulative rate of LNB was 19.6%, 18.3% in homologous IUI and 39.0% in heterologous IUI. The LNB rate was 10.0% at the first cycle, 5.8% at the second cycle, 3.7% at the third or more cycles. When separating by heterologous IUI, it increases to 24.4% in the first cycle and 14.6% in the second cycle. The LNB rate is significantly better in patients under 35 years of age (23.7%) and with a BMI less than 29 (20.8%). CONCLUSIONS: Treatment of low complexity in selected infertile patients is a current therapeutic option with an acceptable rate of LNB per inseminated cycle. The results are influenced by age and BMI.

Prevention of Premature Ovulation by Administration of Gonadotropin Releasing Hormone Antagonist the day After Ovulation Triggering in Diminished Ovarian Reserve Patients / Prevenção da ovulação prematura por meio da administração de antagonismo de liberação de gonadotropismo no dia seguinte à ovulação

Abstract Objective The aim of the present retrospective study was to investigate the effectiveness of single-dose gonadotropin releasing hormone (GnRH) antagonist administration, the day after human chorionic gonadotropin (hCG) triggering for final oocyte maturation, on the prevention of premature luteinization in patients with diminished ovarian reserve in in-vitro fertilization (IVF) cycles. The secondary objective of the study was to search the effect of this protocol on pregnancy outcomes. Methods This is a retrospective study including 267 infertile patients who have single antral follicle seen with ultrasonography on the 2nd or 3rd day of the menstrual cycle before starting IVF treatment. We randomized patients into two groups. The case group comprised patients who had single-dose GnRH antagonist injection the day after hCG triggering formed, and the patients who had the standard treatment regime formed the control group. In both groups, the oocytes were collected 36 hours after hCG injection. Results The premature ovulation rate was significantly low in the case group compared with the control group (6.86 versus 20.6% per scheduled cycle) (p=0.022). Also, the oocyte retrieval rate (93.14 versus 67.87% per scheduled cycle) (p=0.013), the oocyte maturity rate (79.42 versus 47.87%) (p=0.041), the fertilization rate (65.68 versus 34.54%) (p=0.018), and the embryo transfer rate per scheduled cycle (44.11 versus 18.78%) (p=0.003) were higher in the GnRH antagonist group than in the control group. Conclusion The administration of GnRH antagonist the day after hCG trigger in IVF treatments of patients with diminished ovarian reserve enabled a significant decrease in the rate of premature ovulation but had no effect on live birth rate.

Resumo Objetivo O objetivo do presente estudo retrospectivo foi investigar a eficácia da administração do antagonista do hormônio liberador da gonadotrofina (GnRH) em dose única no dia seguinte ao desencadeamento da gonadotrofina coriônica humana (hCG) para a maturação final do oócito, na prevenção da luteinização prematura em pacientes com diminuição do ovário reserva em ciclos de fertilização in vitro (FIV). O objetivo secundário do estudo foi pesquisar o efeito deste protocolo nos resultados da gravidez. Métodos Trata-se de um estudo retrospectivo incluindo 267 pacientes inférteis que apresentam um único folículo antral visto por ultrassonografia no 2° ou 3° dia do ciclo menstrual antes de iniciar o tratamento de FIV. Nós randomizamos os pacientes em dois grupos. Os pacientes que receberam injeção de antagonista de GnRH em dose única no dia seguinte ao desencadeamento do hCG formaram o grupo caso, e os pacientes que receberam o regime de tratamento padrão formaram o grupo controle. Em ambos os grupos, os oócitos foram coletados 36 horas após a injeção de hCG. Resultados A taxa de ovulação prematura foi significativamente baixa no grupo caso em comparação com o grupo controle (6,86 versus 20,6% por ciclo programado) (p=0,022). Além disso, a taxa de recuperação de oócitos (93,14 versus 67,87% por ciclo programado) (p=0,013), a taxa de maturidade do oócito (79,42 versus 47,87%) (p=0,041), a taxa de fertilização (65,68 versus 34,54%) (p=0,018) e a taxa de transferência de embriões por ciclo programado (44,11 versus 18,78%) (p=0,003) foram maiores no grupo antagonista de GnRH do que no grupo controle. Conclusão A administração de antagonista de GnRH, no dia seguinte ao desencadeamento de hCG em tratamentos de FIV de pacientes com reserva ovariana diminuída permitiu uma redução significativa na taxa de ovulação precoce,mas não teve efeito na taxa de nascidos vivos.

Is There Any Effect of the Physician Performing Embryo Transfer in IVF-ICSI Treatment: A Prospective Cohort Study / Existe algum efeito domédico que realiza a transferência de embriões no tratamento de FIV-ICSI: Um estudo de coorte prospectivo

Abstract Objective To evaluate whether there is an effect of the physician who transfers the embryos on pregnancy rates in in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) treatment. Methods A total of 757 participants were analyzed between 2012 and 2017. Participants were classified according to 3 physicians who transferred the embryos: ([group 1=164 patients]; [group 2=233 patients]; [group 3=360 patients]). Baseline parameters and IVF-ICSI outcomes were compared between the groups. Results No differences were determined between the groups regarding the baseline parameters (age, age subgroups [20-29, 30-39, and ≥ 40 years old)], body mass index (BMI), smoking status, infertility period, cause of infertility, baseline follicle stimulating hormone, luteinizing hormone, estradiol (E2), thyroid stimulating hormone, prolactin levels, antral follicle count, duration of stimulation, stimulation protocol, gonadotropin dose required, maximum E2 levels, progesterone levels, endometrial thickness on human chorionic gonadotropin (hCG) administration and transfer days (p>0.05). The numbers of oocytes retrieved,metaphase II (MII), 2 pronucleus (2PN), transferred embryo, fertilization rate, day ofembryo transfer, the catheter effect and embryo transfer technique, and clinical pregnancy rates (CPRs) were also comparable between the groups (p>0.05). Conclusion Our data suggests that the physician who transfers the embryos has no impact on CPRs in patients who have undergone IVF-ICSI, but further studies with more participants are required to elucidate this situation.

Resumo Objetivo Avaliar se há ou não efeito do médico que realiza a transferência de embriões nas taxas de gravidez no tratamento com fertilização in vitro-injeção intracitoplasmática de espermatozoide (FIV-ICSI, na sigla em inglês). Métodos Um total de 757 participantes foram analisados entre 2012 e 2017. Os participantes foram classificados de acordo com 3 médicos que transferiram os embriões: ([grupo 1=164 pacientes]; [grupo 2=233 pacientes]; [grupo 3=360 pacientes]). Parâmetros basais e resultados de FIV-ICSI foram comparados entre os grupos. Resultados Nenhuma diferença foi determinada entre os grupos nos parâmetros basais (idade, subgrupos de idade [20-29, 30-39 e ≥ 40 anos)], índice de massa corporal (IMC), tabagismo, período de infertilidade, causa da infertilidade, hormônio folículo estimulante basal , hormônio luteinizante, estradiol (E2), hormônio estimulador da tireoide, níveis de prolactina, contagem de folículos antrais, duração da estimulação, protocolo de estimulação, dose de gonadotrofina necessária, níveis máximos de E2, níveis de progesterona e espessura endometrial na administração de hCG e nos dias de transferência (p>0,05). O número de oócitos recuperados, MII e 2PN, embrião transferido, taxa de fertilização, dia da transferência do embrião, o efeito do cateter e a técnica de transferência de embrião e taxas clínicas de gravidez (RCPs) também foram comparáveis entre os grupos (p>0,05). Conclusão Nossos dados sugerem que o médico que transfere os embriões não tem impacto sobre as RCPs em pacientes que se submeteram a FIV-ICSI, mas mais estudos com mais participantes são necessários para elucidar esta situação.

Oral dydrogesterone in frozen-thawed embryo transfer cycles

SUMMARY OBJECTIVE: The aim of this study was to compare the use of micronized vaginal progesterone and oral dydrogesterone in the endometrial preparation for frozen-thawed embryo transfer. METHODS: This was a randomized, controlled, open, two-armed clinical trial, with women undergoing frozen-thawed embryo transfer along with hormone replacement therapy for endometrial preparation, between September 2019 and February 2021. A total of 73 patients were randomly selected and orally administered 40 mg/day dydrogesterone (dydrogesterone group, n=36) or 800 mg/day micronized vaginal progesterone (micronized vaginal progesterone group, n=37), after endometrial preparation with transdermal estradiol. The main outcome was a viable ongoing pregnancy with 12 weeks of gestation as evaluated by ultrasound. RESULTS: The reproductive outcomes in frozen-thawed embryo transfer cycles were similar, with pregnancy rates in the dydrogesterone and micronized vaginal progesterone treatment groups being, respectively, 33.3 and 32.4% at 12 weeks pregnancy (confidence interval= -22.4-20.6, p=0.196). CONCLUSIONS: The use of oral dydrogesterone may be a more patient-friendly approach to endometrial preparation in frozen-thawed embryo transfer cycles, avoiding undesirable side effects and discomfort resulting from vaginal administration, while also providing similar reproductive results.

Impact of inactivated SARS-CoV-2 vaccination on embryo ploidy: a retrospective cohort study of 133 PGT-A cycles in China

BACKGROUND: Unsubstantiated concerns have been raised on the potential correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infertility, leading to vaccine hesitancy in reproductive-aged population. Herein, we aim to evaluate the impact of inactivated SARS-CoV-2 vaccination on embryo ploidy, which is a critical indicator for embryo quality and pregnancy chance. METHODS: This was a retrospective cohort study of 133 patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) cycles with next-generation sequencing technology from June 1st 2021 to March 17th 2022 at a tertiary-care medical center in China. Women fully vaccinated with two doses of Sinopharm or Sinovac inactivated vaccines (n = 66) were compared with unvaccinated women (n = 67). The primary outcome was the euploidy rate per cycle. Multivariate linear and logistic regression analyses were performed to adjust for potential confounders. RESULTS: The euploidy rate was similar between vaccinated and unvaccinated groups (23.2 ± 24.6% vs. 22.6 ± 25.9%, P = 0.768), with an adjusted ß of 0.01 (95% confidence interval [CI]: -0.08-0.10). After frozen-thawed single euploid blastocyst transfer, the two groups were also comparable in clinical pregnancy rate (75.0% vs. 60.0%, P = 0.289), with an adjusted odds ratio of 6.21 (95% CI: 0.76-50.88). No significant associations were observed between vaccination and cycle characteristics or other laboratory and pregnancy outcomes. CONCLUSIONS: Inactivated SARS-CoV-2 vaccination had no detrimental impact on embryo ploidy during in vitro fertilization treatment. Our finding provides further reassurance for vaccinated women who are planning to conceive. Future prospective cohort studies with larger datasets and longer follow-up are needed to confirm the conclusion.

Severity of intrauterine adhesions and pregnancy success rates after treatment: Comparison of adhesions obtained from open myomectomy versus uterine curettage

Intrauterine adhesions (IUA) are rare. A retrospective comparative study was conducted between January 1, 2015, and December 31, 2018. Group A comprised 117 women who developed IUAs after open myomectomy, while Group B comprised 113 women who developed IUAs following uterine trauma caused by uterine instrumentation after a termination of pregnancy (TOP) or spontaneous miscarriage. The IUA grade and pregnancy rates and outcomes were compared using the March classification system. All patients underwent hysteroscopic adhesiolysis. The adhesions tended to be more severe (45/117, 38.5%) in Group A than in Group B (29/113, 25.7%); however, this difference was not statistically significant (Chi-Suare 5.047; p = .080). The period of observation was 24 months from the last hysteroscopy. The pregnancy rate in Group A (26, 22.2%) was significantly lower than in Group B (46, 40.7%) (OR: 2.403, 95% CI: 1.352­4.271; p = .003). Open myomectomy was the preceding aetiological factor in a greater proportion of women with IUA in our study. In cases where pregnancy is desired after open myomectomy, especially where the endometrial cavity is breached, postoperative hysteroscopy to exclude IUAs is recommended.

Improving the health and treatment success rates of in vitro fertilization patients with traditional Chinese medicine: Need for more robust evidence and innovative approaches / 中西医结合学报

Maximising access to and the success of fertility treatments should be a priority for global reproductive health, as should overall patient well-being. The demand for in vitro fertilization (IVF) and other assisted fertility treatments has increased over the past decade and is likely to further increase in years to come. Nevertheless, there is still considerable unmet demand for infertility support worldwide. Moreover, the high emotional, physical and financial burden experienced by individuals undergoing IVF cycles can be a risk for their mental and physical health, which in turn can influence treatment continuation and the likelihood of IVF success. Studies from various parts of the world show that most individuals undergoing IVF also use adjunct alternative medicines and procedures, the most common being traditional Chinese medicine (TCM). The complementary and synergistic role of TCM for individuals undergoing IVF is an area that merits further attention and research, both for its potential positive effects on IVF success rates and for its broader physical and mental health benefits. However, much of the existing evidence is not sufficiently robust or consistent for findings to be adopted with confidence. This commentary argues that much work must be done to understand the efficacy and clinical best practices for these integrated approaches. This can be achieved in part by developing more robust and clinically relevant randomized controlled trial protocols, collecting and triangulating evidence through a variety of study designs and methods, and strengthening the collection and pooling of clinic-level data.

Effect of Acupuncture on Outcomes of in vitro Fertilisation: A Scoping Review / 中国结合医学杂志

OBJECTIVES@#To identify, examine and summarize the available evidence on the effectiveness and safety of acupuncture for in vitro fertilisation (IVF) outcomes.@*METHODS@#Eight electronic databases, including PubMed, EMBASE, Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database and VIP Database, were searched, supplemented by manual searches. Two researchers independently conducted the literature screening, data extraction, and methodological quality assessments. A narrative description was provided to show the general information and specific characteristics of the included studies. A bubble plot was used to visually display the overall effects of acupuncture on IVF outcomes.@*RESULTS@#Eighty-two studies were identified, including 64 primary studies and 18 systematic reviews. Transcutaneous electrical acupoint stimulation, electric acupuncture and manual acupuncture were applied in most studies and compared with no acupuncture, sham acupuncture and placebo acupuncture control groups. Sixty-three (98.4%) primary studies reported clinical pregnancy rate, and positive effects of acupuncture were found in 34 studies (54.0%). Live birth rate was reported in only 18 (28.1%) primary studies, of which 10 (55.6%) showed positive results. In addition, only 8 and 2 systematic reviews showed that acupuncture could increase clinical pregnancy events and live birth events, respectively. However, none of these reviews was of high methodological quality.@*CONCLUSIONS@#Available evidence suggests that acupuncture therapy could improve clinical pregnancy rates. However, whether acupuncture could increase live birth events was difficult to determine based on the few studies that have reported this outcome indicator. Furthermore, the methodological quality of most systematic reviews was assessed as critically low or low. Studies with a rigorous design and standardized implementation should be performed to refine the available evidence.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology / 亚洲男科学杂志(英文版)

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.

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.

Intrauterine insemination with donor sperm: only the number of motile spermatozoa inseminated influences both pregnancy and live-birth rates / 亚洲男科学杂志(英文版)

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.

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.

Effect of acupuncture on pregnancy outcomes of frozen embryo transfer in patients with anovulatory infertility / 中国针灸

OBJECTIVE@#To observe the effect of conventional ovulation induction protocol and acupuncture combined with conventional ovulation induction protocol on pregnancy outcomes of frozen embryo transfer (FET) in patients with anovulatory infertility.@*METHODS@#A total of 60 patients with anovulatory infertility were randomized into an observation group and a control group, 30 cases in each group. In the control group, conventional ovulation induction protocol was applied to prepare endometrium. On the basis of the control group, acupuncture was started on the 2nd day of menstrual cycle in the observation group，Baihui (GV 20), Mingmen (GV 4), Geshu (BL 17), Guanyuan (CV 4), Qihai (CV 6), etc. were selected, once every other day, until 1 day before transplantation. The clinical pregnancy rate, embryo implantation rate, endometrial morphology on HCG trigger day, ovulation rate and cycle cancellation rate were compared in the two groups. The endometrial thickness before treatment and on HCG trigger day, TCM symptom score before and after treatment were observed in the two groups.@*RESULTS@#In the observation group, the embryo implantation rate and clinical pregnancy rate were higher than the control group (P<0.05), endometrial thickness and endometrial morphology on HCG trigger day were superior to the control group (P<0.05). After treatment, the TCM symptom score in the observation group was decreased compared with before treatment (P<0.05), and the variation was greater than the control group (P<0.01).@*CONCLUSION@#On the basis of the conventional ovulation induction protocol, acupuncture could enhance the embryo implantation rate and clinical pregnancy rate of FET, improve the endometrial receptivity of patients with anovulatory infertility.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evalvate efficacy of Qizi Yusi Pills (QYP), a Chinese medicine compound preparation, on in vitro fertilization-embryo transfer (IVF-ET) in women of advanced reproductive age.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled trial was conducted from June 2018 to October 2019. A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design, with 62 patients in each group. All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist (GnRH-a) long protocol. As the QYP group, QYP was administered while the control group received placebo. QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval. Both medications were taken orally at doses of 10 g three times each day. The primary outcome was cumulative pregnancy rate, and the secondary outcomes were periodic medication, follicular status, serum hormone and endometrial receptivity. Follow-up continued until 4 weeks after delivery. Maternal and neonatal complications, such as gestational diabetes, were also observed.@*RESULTS@#Overall, 119 patients completed the study, 60 in the QYP group and 59 in the placebo group. Per protocol (PP) analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group [43.33% (26/60) vs. 25.42% (15/59), P=0.040). Additionally, more oocytes were retrieved from the QYP group than those from the placebo group (8.95 ± 3.12 vs. 7.85 ± 1.91, P=0.022). Moreover, the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group (11.78 ± 2.27 mm vs. 10.68 ± 2.07 mm, P=0.012). Maternal and neonatal complications between the two groups were not significantly different (P>0.05). Intention-to-treat analysis was in line with PP results.@*CONCLUSIONS@#QYP can enhance ovarian reserve capacity and ovarian response, and possibly promote endometrial receptivity. QYP effectively improves cumulative pregnancy rates in older patients (⩾35 years) undergoing IVF-ET. (Registration No. ChiCTR1800014427).

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 lactation number and parity on milk yield of Saanen goat's breed / [Influência do número de lactação e paridade na produção de leite da raça de cabras Saanen]

The aim of this research was to determine the influence of lactation number and parity on milk yield of Saanen goat's breed. It has been concluded that milk yield was higher for goats that had given birth to twins and three kids than for goats that had given birth to a single kid (P<0.05). The longevity has a great positive impact on production, given that goats in the fifth lactation produced more milk than goats in first or second lactation (P<0.05), while goats in the sixth lactation still produced more milk than goats in first lactation (P<0.05). During the period from 2014- 2019, the research was conducted on a farm of multiparous Saanen goats in Vojvodina (northern part of Serbia). In the observed period, the farm had between 350 and 400 goats per milking, and the research included a total of 1,628 concluded lactations, within which the first lactations were the most 484, then the second 381. According to the number of lactations, goats were grouped into classes from one to seven and from one to three for parity. By comparing each individual lactation, it was determined that in first lactation goats produced significantly lower milk than goats in the rest lactations(P<0.05), except the seventh. Research has shown that lactation number has a significant influence on milk yield (P=0.00). Increasing the fertility of goats significantly affects the production capacity of dairy goats, since does with a larger number of kids in the litter had a significantly higher milk production (P<0.05). Due to the larger number of kids in the litter, milk production also increases. Likewise, it is assumed that the increase in milk yield of goats with two and three kids is a consequence of a larger placenta, i.e. stronger lactogenic activity during pregnancy.(AU)

O objetivo desta pesquisa foi determinar a influência do número de lactações e da paridade na produção de leite da raça de cabras Saanen. Concluiu-se que a produção de leite era maior para caprinos que haviam dado à luz gêmeos e três cordeiros do que para caprinos que haviam dado à luz um único cordeiro (P<0,05). A longevidade tem um grande impacto positivo na produção, dado que as cabras na quinta lactação produziram mais leite do que as cabras na primeira ou segunda lactação (P<0,05), enquanto as cabras na sexta lactação ainda produziram mais leite do que as cabras na primeira lactação (P<0,05). Durante o período de 2014- 2019, a pesquisa foi realizada numa fazenda de cabras Saanen multipares em Voivodina (parte norte da Sérvia). No período observado, a fazenda tinha entre 350 e 400 cabras por ordenha, e a pesquisa incluiu um total de 1.628 lactações concluídas, dentro das quais as primeiras lactações foram as mais 484, depois as segundas 381. De acordo com o número de lactações, as cabras foram agrupadas em classes de um a sete e de um a três para paridade. Comparando cada lactação individual, determinou-se que na primeira lactação as cabras produziram leite significativamente menor do que as cabras nas demais lactações (P<0,05), exceto a sétima. Pesquisas mostraram que o número de lactações tem uma influência significativa na produção de leite (P=0,00). O aumento da fertilidade das cabras afeta significativamente a capacidade de produção de caprinos leiteiros, já que com um número maior de cabritos na ninhada a produção de leite foi significativamente maior (P<0,05). Devido ao maior número de cabritos na ninhada, a produção de leite também aumenta. Da mesma forma, assume-se que o aumento na produção de leite de cabras com dois e três cabritos é uma consequência de uma placenta maior, ou seja, de uma atividade lactogênica mais forte durante a gestação.(AU)

Implementación de técnicas de reproducción asistida en el Centro de Reproducción Humana de la Universidad de Valparaíso: resultados del primer trienio (2015 - 2017) / Implementation of assisted reproduction techniques at the Center of Human Reproduction of the Universidad de Valparaíso: results of the first triennium (2015 - 2017)

INTRODUCCIÓN Y OBJETIVOS: La infertilidad es una enfermedad altamente prevalente que afecta aproximadamente a un 8-10% de las parejas en edad reproductiva. Las Técnicas de Reproducción Asistida (TRA) han experimentado un importante incremento en el número de tratamientos realizados, no obstante, el acceso en Chile sigue siendo limitado y centralizado. El presente estudio resume la experiencia y los resultados de TRA del primer trienio del Centro de Reproducción Humana de la Universidad de Valparaíso (CRHUV). MÉTODOS: Estudio de cohorte retrospectiva de las pacientes sometidas a TRA en el CRHUV desde 1 de enero de 2015 a 31 diciembre 2017. Se realizó un análisis descriptivo e inferencial. La distribución de variables fue analizada con la prueba de Shapiro-Wilk. Para variables cualitativas se usó la prueba exacta de Fisher. RESULTADOS: Se iniciaron un total de 581 ciclos. Para un total de 340 ciclos en fresco con ovocitos propios, la tasa de embarazo (TE) y de parto (TP) por ciclo aspirado fue de 43,5% y 36,7% respectivamente. En el mismo grupo, la TE y TP por transferencia embrionaria fue de un 48,4% y un 40,9% respectivamente, siendo superior al comparar transferencia doble con un embrión (p < 0,05). También se observó un aumento de TE en menores de 35 años (p < 0,05). La TE y TP por transferencia embrionaria fue semejante en transferencia de embriones frescos y congelados. Al transferir embriones producto de ovocitos donados se observó un incremento significativo de la TE y TP con tasas de 73,1% y 61,5% respectivamente. Las tasa globales y estratificadas de embarazo y parto fueron comparables en el trienio estudiado con los resultados de la REDLARA. CONCLUSIÓN: La exitosa implementación del CRHUV se respalda en los resultados comparables a lo reportado por literatura internacional.

INTRODUCTION AND OBJECTIVES: Infertility is a highly prevalent disease that affects approximately 8-10% of couples in reproductive age. Assisted reproduction techniques (ART) have experienced a significant increase in the number of treatments performed, however, access in Chile remains limited and centralized. This study summarizes the experience and results of the first triennium of the Center for Human Reproduction of the Universidad de Valparaíso (CRHUV). METHODS: Retrospective cohort study of patients undergoing ART at the CRHUV from January 1, 2015 to December 31, 2017. A descriptive and inferential analysis was performed. The distribution of the variables was analyzed with the Shapiro-Wilk test. For qualitative variables, Fisher's exact test was used. RESULTS: A total of 581 cycles were started. For a total of 340 fresh cycles with own oocytes, the pregnancy (RP) and delivery (DR) rate per oocyte retrival was 43.5% and 36.7%. In the same group, PR and DR per embryo transfer was 48.4% and 40.9%, being higher when comparing double with a single embryo transfer (p <0.05). A higher PR was also observed in < 35 years patients (p <0.05). The PR and DR per embryo transfer was similar using fresh and frozen embryo. In oocytes donation, a significant increase in PR and RD per embryo transfer was observed with rates of 73.1% and 61.5%, respectively. The global and stratified rates of pregnancy and delivery were comparable in the studied triennium compared to the results of REDLARA. CONCLUSION: The successful implementation of the CRHUV is supported by results comparable to those reported by international literature.