The Impact of Seasonal Variation on Clinical Pregnancy and Live Birth Rates in Assisted Reproductive Technology: A Retrospective Cohort Study in Hainan

Objective:To investigate the influence of season on live birth and clinical pregnancy rates,as well as assisted reproductive technology(ART)outcomes,in the Hainan region.Methods:Patients were categorized into four groups based on the dates of artificial insemination and transplantation:spring,summer,autumn,or winter.The main outcome measures were clinical pregnancy rates and live birth rates.Secondary outcomes included body mass index(BMI),oocyte number,two pronuclei(2PN)cleavage rate,total gonadotropin(Gn)dosage and days,age,2PN fertilization rate,sperm concentration,sperm PR rate,anti-Müllerian hormone(AMH),and endometrial thickness.Outpatient semen quality indicators included sperm PR rate,total sperm count,sperm concentration,and total sperm motility.Results:This retrospective cohort study analyzed 2,016 artificial insemination cycles and 1,783 ovarian retrieval cycles from January 2017 to October 2022,and assessed the semen quality of 6,651 outpatients from May 2017 to October 2022.In artificial insemination cycles,sperm PR rate and clinical pregnancy rate were highest in winter,with a statistically significant difference between groups(P<0.05).Clinical pregnancy rate was influenced by both age and sperm PR rate(P<0.05).In ovarian retrieval cycles,the winter group had significantly higher clinical pregnancy,2PN fertilization,and 2PN cleavage rates than the other groups.The autumn group had higher live birth rates,though not significantly different.Additionally,winter months showed higher total sperm concentration and total sperm number compared to other seasons.Conclusion:Seasonality affected clinical pregnancy and live birth rates in artificial insemination cycles but not in ovarian retrieval cycles in the Hainan region.These findings suggest that while there is no need to choose a specific season for ovarian retrieval cycles,artificial insemination in winter may be preferable for patients.

Embryo quality and chromosomal abnormality in embryos from couples undergoing assisted reproductive technology using preimplantation genetic screening

Objective:To detect common chromosomal aneuploidy variations in embryos from couples undergoing assisted reproductive technology and preimplantation genetic screening and their possible associations with embryo quality.Methods:In this study,359 embryos from 62 couples were screened for chromosomes 13,21,18,X,and Y by fluorescence insitu hybridization.For biopsy of blastomere,a laser was used to remove a significantly smaller portion of the zona pellucida.One blastomere was gently biopsied by an aspiration pipette through the hole.After biopsy,the embryo was immediately returned to the embryo scope until transfer.Embryo integrity and blastocyst formation were assessed on day 5.Results:Totally,282 embryos from 62 couples were evaluated.The chromosomes were normal in 199(70.57%)embryos and abnormal in 83(29.43%)embryos.There was no significant association between the quality of embryos and numerical chromosomal abnormality(P=0.67).Conclusions:Embryo quality is not significantly correlated with its genetic status.Hence,the quality of embryos determined by morphological parameters is not an appropriate method for choosing embryos without these abnormalities.

Support from Healthcare Professionals for Couples/Partners Undergoing Assisted Reproductive Technology in Japan: A Literature Review

Background and Purpose: A growing number of couples/partners have been undergoing assisted reproductive technology (ART) in Japan. The purpose of this study was to clarify the support from healthcare professionals based on the support vectors in the Family Care/Caring Theory proposed by Hohashi (2015) through a literature review. Methods: Using Ichushi-Web, we searched for original articles using the keywords “assisted reproductive technology”, “infertility”, “family”, “couple”, “nursing”, “care”, and “support”. Thirteen articles suitable for the purpose of this study were subjected to content analysis. Family support was encoded and grouped into subcategories and categories, and classified according to support vectors. Results: A total of 21 categories of support from healthcare professionals was extracted. Intervention for family internal environment included seven categories, such as “Nursing professionals stay close to females”. Intervention for family system unit included five categories, such as “Nursing professionals adjust couple/partner relationships”. Intervention for micro system only included “Nursing professionals provide opportunities for peer support to the couples/partners” and intervention for macro system only included “Nursing professionals encourage medical doctors to relate to females”. Intervention for family chrono environment included seven categories, such as “Healthcare professionals resolve female’s anxieties”. Conclusion: The support from healthcare professionals could be organized by the support vectors of Family Care/Caring Theory, but intervention for supra system (culture, religion, etc.) was lacking. Moreover, because most support was directed toward females or couples/partners, male-focused direct and/or indirect support are also needed. .

Assisted Reproductive Technology for HIV-1 Serodiscordant Couples: A Review of Current Controversies

Since 1992, assisted reproductive technology （ART） has been reported as a viable means of helping HIV-1 serodiscordant couples achieve pregnancy while theoretically reducing the risk for viral transmission. While the sum of the evidence suggests that ART is effective and safe, numerous controversies still exist, The follow- ing review addresses several of the important issues involved in the use of ART for HIV-serodiscordant couples, including patient selection, semen processing techniques, post-process HIV testing, the use of lUI vs IVF-ICSI.

Clinical study of different fertilization methods of assisted reproductive technology on neonatal birth defects

Objective:To investigate the incidence of neonatal birth defects in assisted reproductive technology(ART)by in vitro fertilization(IVF)and intracytoplasmic sperm injection(ICSI).Methods:The clinical data of 4229 cases of singleton deliver by infertile patients under 35 years old who received IVF/ICSI-ET in our center were analyzed.According to different fertilization methods,they were divided into IVF group(2967 cases)and ICSI group(1262 cases).The general situation of birth,birth defects and the location of defects were compared between the two groups.Results:a total of 38 cases of neonatal birth defects were found,the incidence of birth defects was 0.89%,including 30 cases(1.01%)in IVF group and 8 cases(0.64%)in ICSI group.There was no significant difference in the incidence of birth defects between the two groups(P>0.05).There was also no significant difference in birth weight,gestational age and gender ratio between the two groups(P>0.05).Conclusion:Different fertilization methods in assisted reproductive technology do not increase the incidence of neonatal birth defects.

Implementation and Evaluation of Infertility Reflection in Early Pregnancy after the Use of Assisted Reproductive Technology: A Feasibility Study

Background: This study aims to evaluate the infertility reflection in early pregnancy after assistive reproductive therapy (ART), including 1) process evaluation (the use and evaluation of infertility reflection) and 2) outcome evaluation (satisfaction of care needs, anticipatory anxiety towards the loss of a pregnancy or fetus, cognition of infertility experience, and depression and anxiety). Methods: This program evaluation study used a one-group pre-post-test design. The participants were 50 primiparas who had undergone ART at two fertility treatment facilities in a metropolitan area in Japan. For the infertility reflection, they conducted an online reflection. Data were collected three times: at the 5th week of pregnancy (Time 1), the 8th week of pregnancy as the final consultation at the clinic (Time 2), and the 16th week of pregnancy as the final point of early pregnancy (Time 3). Results: The data from 40 participants were analyzed. More than 80% of the users of the online reflection positively evaluated the appropriateness and usefulness of the methods and contents. Organized thoughts and feelings by reflection were shown as the reasons for the usefulness. The evaluation of the online reflection showed a relatively strong correlation with the Care Need Satisfaction Scale (CNSS) for both Time 2 and Time 3, but the online reflection did not show a significant correlation with the other outcome variables. There were no significant differences in outcome variables between users and non-users of online reflection between Time 2 and Time 3. Conclusions: Attempts at the reflection in early pregnancy require modified methods that do not have a negative impact and lead to the fulfillment of needs.

Pregnancies Outcome after Assisted Reproductive Technology: A Multicenter Case Control Study in a Low Income Setting Douala, Cameroon

The objective was to assess the outcome of pregnancies after assisted reproductive technology (ART). It was a case-control study carried out in four health facilities in Douala-Cameroon, over a period of five years. The cases were pregnant women who conceived through ART and the controls were those who conceived naturally. Cases and controls were matched for maternal age and parity (one case for two controls). A logistic regression analysis was used to compute Odds ratios. Statistical significance was set at 0.05. A total of 174 women who conceived through ART and 348 who conceived naturally were enrolled. Some independent factors associated with ART were: age over 45 years [aOR: 7.55; 95% CI (1.55 - 36.76);p: 0.01], twin pregnancies [aOR: 16.55; 95% CI (7.91 - 34.60);p < 0.01], Cervical cerclage [aOR: 3.04; 95% CI (1.23 - 7.50);p: 0.01], miscarriages [aOR: 11.73; 95% CI (5.07 - 27.10);p: 0.01], elective cesarean section [aOR: 4.63; 95% CI (2.27 - 9.45);p: 0.01] and low birth weight [aOR: 3.32; 95% CI (1.90 - 5.82);p < 0.01]. Women who conceived by ART were older with higher rates of multiple pregnancy and complications. We recommend transfer of a single embryo.

Impacts of assisted reproductive technology on perinatal outcomes and offspring health

Assisted reproductive technology(ART)has evolved rapidly over the last 40 years,offering hope to individuals and couples struggling with infertility.As technology continues to evolve,simulating a realistic female reproductive system environment has become a common goal for all types of ARTs,thereby reducing the impact of the artificial microenvironment on perinatal and offspring health.In this review,we provide a brief history of the development of each major ART and discuss the impact of ART on perinatal and offspring health.We also explore how the negative consequences of ART may be overcome and how its benefits can be maximized.

Influence of assisted reproductive technology and uterine leiomyoma on pregnancy outcomes in women with adenomyosis

Aim To assess whether adverse pregnancy outcomes in women with adenomyosis are different according to the method of conception and the concurrent of uterine leiomyoma(UL).Methods We performed a retrospective study.Fifty-three singleton pregnancy cases complicated with adenomyosis were included in this study.In the study group,15 women became pregnant with assisted reproductive technology(ART)and 21 women combined with UL.Pregnancy outcomes were compared between ART and non-ART,UL and non-UL groups.Results The prevalence for such complications as hypertensive disorder complicating pregnancy(HDCP)and postpartum hemorrhage(PPH)were significantly higher in the women conceived by ART(33.3%vs.5.3%,P​=​0.023)and(53.3%vs.23.7%,P​=​0.037),respectively.And women concurrent with UL of which the diameter≥4​cm were more likely to have severe PPH(44.4%vs.0%,P​=​0.021).Conclusion ART may increase the risk of adverse pregnancy outcomes such as HDCP and PPH in women with adenomyosis and UL of which the diameter≥4​cm may further increase the risk of severe PPH.

Cerebral palsy in children born after assisted reproductive technology: a meta-analysis

Background Several studies have assessed the association between cerebral palsy(CP)and assisted reproductive technology(ART),but the results remain controversial.We conducted a meta-analysis to evaluate the risk of CP after ART compared with natural conceptions and to examine CP risk separately in ART singletons,multiples and preterm births.Methods Web-based databases(PubMed,Embase,the Cochrane Library,and Web of Science)were searched until November 22,2020.Studies which compare CP rates after ART with natural conceptions were included.The Newcastle–Ottawa Scale was used to assess the quality of the included studies.Effect estimates were extracted and combined using the fixed-effects or random-effects model depending on the heterogeneity test.Results There were nine studies included in the meta-analysis.The included studies were of moderate or high quality.A significantly higher risk of CP[odds ratio(OR)=2.17,95%confidence interval(CI)1.72–2.74]was found in ART children(n=89,214)compared with naturally conceived children(n=4,160,745).The significantly higher risk decreased when data were restricted to singletons(OR=1.36,95%CI 1.16–1.59)and disappeared when data were restricted to multiples(OR=1.05,95%CI 0.86–1.29)or preterm births(OR=1.53,95%CI 0.66–3.56).Subgroup and sensitivity analyses indicated that the overall results were robust.Conclusions The risk of CP is increased more than two-fold after ART.This increased risk is largely due to increased rates of multiple birth and preterm delivery in ART children.

Cost-effectiveness of varicocele surgery in the era ot assisted reproductive technology

The advent of innovative techniques for addressing infertility has made for exciting times in the arena of andrology. The success of microTESE for retrieving sperm has enabled azoospermic men to have the opportunity to father biological children when it was previously impossible. The ability to offer a variety of assisted reproductive techniques that includes intracytoplasmic sperm injection has opened the door for couples with male factor infertility who were otherwise untreatable. With the multitude of options available to infertile couples, however, comes an unsurprising degree of controversy regarding what treatments should be offered and when. Complicating the picture is the question of if and when varicocele repair should be undertaken, and the financial implications of the treatment decisions that are made. The infertile couple with varicocele warrants careful consideration. The overall efficacy of varicocele repair as well as cost-effectiveness of repair compared to immediate microTESE in azoospermic men and assisted reproductive technology in men with suboptimal semen parameters will be reviewed.

Outcome of conservative treatment and subsequent assisted reproductive technology for patients with early-stage endometrial adenocarcinoma and poor fertility potential

Conservative treatment with high doses of progestin is an alternative to standard hysterectomy for young patients with early-stage endometrial adenocarcinoma who desire to preserve their fertility. Here we report a patient with well-differentiated early-stage endometrial adenocarcinoma and poor fertility potential who failed to become pregnant in two in vitro fertilization-embryo transfer cycles and suffered a relapse after conservative treatment. This case illustrates that assessment of fertility potential is critical at the time of initial evaluation and conservative treatment planning for patients with endometrial adenocarcinoma.

Sperm-specific protein ACTL7A as a biomarker for fertilization outcomes of assisted reproductive technology

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.

Imprinting methylation and assisted reproductive technology

Assisted reproductive technology （ART） is an important treatment for infertile people of reproductive age and is also known as fertility treatment. The processes of ART involves the isolation, handling and culture of early embryos, which may result in alterations in genomic methylation at specific loci and influence the proper establishment and maintenance of genomic imprints. Recent studies have identified an increased incidence of imprinting disorders via ART. In this article, we reviewed that the ART may be prone to induction of imprinting methylation errors during embryonic development. Further studies are necessary to elucidate the safety of ART in this field.

Birth Defects in Assisted Reproductive Technology and Spontaneously Conceived Children:A Meta-analysis

Objective To evaluate the risk of birth defects in children born following assisted reproductive technology （ART） and spontaneous conceptions. Methods This study carried out an updated systematic review to identify papers published by August 2013 with data relating to birth defects of children conceived using ART （IVF and for ICSI） compared with those spontaneously conceived and also compared birth defects between subgroups of lVF and ICSI. Results Totally 76 studies were identified for review. The individual relative risk （RR） estimated for these studies ranged from 0.44 to 5.51, a signifieantly increased risk of birth defects was observed （RR=l.36, 95%CI=1.25-1.47） in ART compared with the spontaneously conceived group, which was also evident in the subgroup analysis. Among these studies, 16 studies simultaneously gave data of birth defects comparing IVF and ICSI children, which showed no difference in risk of combined effects （RR=0.90, 95%CI=0.80 1.02）, but ICSI had a higher risk in subgroups of clinical research （RR=O. 76, 95%CI=0.65-0.89） and crude RR value （RR=O. 78, 95%CI=0.67 0.91）. Conclusion Pooled results from all suitable published studies suggested that children born following ART were at increased risk of birth defects compared with spontaneous conceptions. There is no difference in birth defect risk between children conceived by IVF or 1CS1 using a summative analysis, however, 1CS1 had a significant higher risk in birth defect risk comparing with 1VF when using subgroup analyses of sample size and RR value.

Effects of Luteinizing Hormone Supplementation on Ovarian Response and Assisted Reproductive Technology Outcomes in Antagonist In vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Meta-analysis

Objective:The study objective was to investigate the effects of luteinizing hormone(LH)supplementation on ovarian response and assisted reproductive technology(ART)outcomes in in vitro fertilization/intracytoplasmic sperm injection cycles with a gonadotropin(Gn)-releasing hormone antagonist protocol.Methods:This is a meta-analysis,and nine published randomized controlled trials(1,685 patients)were included.Continuous data were extracted in the form of mean±standard deviation and population size,whereas dichotomous data were extracted in the form of odds ratio.Results:The total amount of follicle-stimulating hormone(FSH)used,the duration of stimulation(DOS),the number of eggs in MII stage,the total number of formed embryos,the clinical pregnancy rate,and live birth rates were similar between groups,but the estrogen level on the day of human chorionic Gn(hCG)administration was slightly higher in the LH supplementation group.On subgroup analysis,it was reported that the addition of LH could significantly increase estrogen levels on the day of hCG administration in patients older than 35 years,and LH supplementation starting on the day of FSH administration may slightly extend the DOS.Moreover,regardless of the timing of LH supplementation,an increase in estrogen levels was found on the day of hCG administration.Conclusions:LH supplementation of an antagonist protocol increases estrogen levels on the day of hCG administration,but does not increase the number of mature oocytes retrieved,and also fails to improve ART outcomes.

The effect of different cancer therapies on clinical outcomes of assisted reproductive technology in breast cancer patients

Objective To evaluate the clinical outcomes of assisted reproductive technology(ART)on fertility preservation and infertility treatment in breast cancer patients who had undergone different cancer therapies.Methods 20 infertile females who had undergone breast cancer treatments during 2011–2018 were studied retrospectively.The patients were divided into two groups based on their cancer treatment methods and their needs of fertility preservation:the combined treatment group,who had both breast cancer surgery combining with any of the three treatments(adjuvant endocrine therapy,radiotherapy or chemotherapy),and the surgery only group.A group of infertile females without breast cancer history were used as a control group.An aromatase inhibitor Letrozole-based ovarian micro-stimulation protocol was used in females from the three groups for in vitro fertilization and embryo transfer.The ART clinical outcomes were evaluated by using the parameters of antral follicle count(AFC),the ratio of FSH/LH,oocyte retrieval number,2 pronucleus(2 PN)fertilization rate,high-quality embryo rate,clinical pregnancy rate,and delivery outcome.Results The surgery only group had significantly lower ratio of FSH/LH than the combined treatment group and the control group.No significant difference on the ART clinical outcomes,evaluated by the aforementioned criteria,were found between the three groups.Conclusions Breast cancer surgery with adjuvant therapies,but not surgery alone,may damage ovarian function.The best time-limited window to preserve fertility for breast cancer patients is after surgery but before the initiation of adjuvant therapies.Importantly,the clinical outcomes of aromatase inhibitor-based ovary micro-stimulation in breast cancer patients are similar to that in non-breast cancer controls.

Long-term follow-up of children conceived through assisted reproductive technology

Children conceived via assisted reproductive technologies (ART) are nowadays a substantial proportion of the population. It is important to follow up these children and evaluate whether they have elevated health risks compared to naturally conceived (NC) children. In recent years there has been a lot of work in this field. This review will summarize what is known about the health of ART-conceived children, encompassing neonatal outcomes, birth defects, growth and gonadal developments, physical health, neurological and neurodevelopmental outcomes, psychosocial developments, risk for cancer, and epigenetic abnormalities. Most of the children conceived after ART are normal. However, there is increasing evidence that ART-conceived children are at higher risk of poor perinatal outcome, birth defects, and epigenetic disorders, and the mechanism(s) leading to these changes have not been elucidated. Continuous follow-up of children after ART is of great importance as they progress through adolescence into adulthood, and new ART techniques are constantly being introduced.

Microfluidic thermotaxic selection of highlymotile sperm and in vitro fertilization

The selection of the most motile and functionally competent sperm is an essential basis for in vitro fertilization(IVF)and normal embryonic development.Widely adopted clinical approaches for sperm sample processing intensely rely on centrifugation and wash steps that may induce mechanical damage and oxidative stress to sperm.Although a few microfluidic sperm sorting devices may avoid these adverse effects by exploiting intrinsic guidance mechanisms of sperm swimming,none of these approaches have been fully validated by clinical-grade assessment criteria.In this study,a microfluidic sperm sorting device that enables the selection of highly motile and functional sperm via their intrinsic thermotaxis is presented.Bioinspired by the temperature microenvironment in the fallopian tube during natural sperm selection,a microfluidic device with controllable temperature gradients along the sperm separation channel was designed and fabricated.This study investigated the optimal temperature conditions for human sperm selection and fully characterized thermotaxis-selected sperm with 45 human sperm samples.Results indicated that a temperature range of 35–36.5℃along the separation channel significantly improves human sperm motility rate((85.25±6.28)%vs.(60.72±1.37)%;P=0.0484),increases normal sperm morphology rate((16.42±1.43)%vs.(12.55±0.88)%;P<0.0001),and reduces DNA fragmentation((7.44±0.79)%vs.(10.36±0.72)%;P=0.0485)compared to the nonthermotaxis group.Sperm thermotaxis is species-specific,and selected mouse sperm displayed the highest motility in response to a temperature range of 36–37.5℃ along the separation channel.Furthermore,IVF experiments indicated that the selected sperm permitted an increased fertilization rate and improved embryonic development from zygote to blastocyst.This microfluidic thermotaxic selection approach will be translated into clinical practice to improve the IVF success rate for patients with oligozoospermia and asthenozoospermia.

Human circBOULE RNAs as potential biomarkers for sperm quality and male infertility

Reliable molecular biomarkers to predict fertility remain scarce.The current study investigated the potential of testis-specific circBOULE RNAs as biomarkers for male infertility and sperm quality.Using reverse transcription-PCR and real-time reverse transcription-PCR assays,we identified seven circular RNAs from the human BOULE gene in human sperm.We observed that the expression level of circEx3-6 was significantly reduced in asthenozoospermia,while the expression levels of both circEx2-6 and circEx2-7 were decreased in terato-zoospermia,compared with the controls.Furthermore,we demonstrated that the expression level of circEx2-6 was negatively correlated with the sperm DNA fragmentation index,and the expression level of circEx2-7 was correlated with both fertilization and cleavage rates in those treated with the assisted reproductive technologies.Further functional analyses in a transgenic fly model supported the roles of circBOULE RNAs in sperm development and human male fertility.Collectively,our findings support that sperm circBOULE RNAs may serve as diagnostic biomarkers for assessing sperm motility and DNA quality.Therefore,clinical application and significance of sperm circBOULE RNAs in the assisted reproductive technologies warrant further investigation.