Assisted Reproductive Technology Cycles Research Articles

Model-based estimation of the health care expenditure and out-of-pocket payment for assisted reproductive technology: A retrospective linkage study using the Japanese national ART registry.

From April 2022, the Japanese government funding system for assisted reproductive technology (ART) has shifted from government subsidies to universal health insurance. To date, studies estimating the health care expenditure for ART are scarce. We estimated health care expenditures for ART cycles and compared the proportion of patients' out-of-pocket payment by ovarian stimulation protocols under the Japanese government subsidy system. We linked payment information for government subsidies in Saitama Prefecture during 2016 and 2017 with the Japanese ART registry. Health care expenditures for all treatment cycles in Japan during 2017 among women aged <43 years (n = 369 757) were estimated using a generalized linear model. We linked 6269 subsidy applications to the Japanese ART registry. The average treatment fee for a fresh cycle was 376 434 JPY (standard deviation = 159 581). However, significant variation was observed across ovarian stimulation protocols. The estimated health care expenditure for ART during 2017 was 101 278 629 888 JPY (920 714 817 USD), leading to a 0.24% increase in the national health care expenditure for fiscal year 2017. Fresh cycles accounted for 70% of the expenditure. The proportion of the average patient out-of-pocket payment for one treatment cycle was smaller for natural (0%) and mild ovarian stimulation using clomiphene citrate (4.5%-20.7%) than those of conventional stimulation (30.3%-32.4%). Health insurance coverage for ART would increase national health care expenditure by 0.24%. Under the subsidy system, the proportion of the average patient out-of-pocket payment was smaller for natural and mild ovarian stimulation than conventional stimulations.

Relationship between Endometrial Thickness and Pregnancy Outcomes in Assisted Reproductive Technology Cycles

ABSTRACT Objective: To explore the relations of different ultrasonic endometrial thickness (EMT)values on hCG trigger day and the pregnancy rate (PR) after fresh embryo transfer (ET) in controlled ovarian stimulation (COS) cycles. Background: Successful implantation and delivery require both the functional embryo and receptive endometrium in assisted reproductive technology (ART) cycles which is an expensive procedure with low implantation and pregnancy rate (PR). It is estimated that embryos account for one-third, and suboptimal endometrial receptivity for the remaining two-thirds of implantation failures. There is still an ongoing debate regarding the predictive ability of ultrasonic endometrial evaluation on the day of human chorionic gonadotrophin (hCG) trigger during controlled ovarian stimulation (COS) on the outcomes of pregnancies after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Method: A retrospective review of data from medical records of all patients who underwent COS, oocyte retrieval, IVF/ICSI, and fresh ET between March 2021and July 2022 at Centre for Fertility and Reproductive Medicine (CFRM), St Paul Millennium medical College (SPHMMC) Addis Ababa, Ethiopia. Patients were categorized based on their ET outcome (as pregnant or non-pregnant) and EMT values on the day hCG trigger (groups A &lt;8mm, B 8-12mm, and C&gt;12 in mm) to study and analyze if any relation between endometrial thickness and pregnancy rate existed. Results: A total of 548 records were analyzed. PR was 40.9%. The odds of pregnancy were higher among patients with EMT group B (82.8% vs 74.6%, p=0.05) and was shown to be significant after controlling for the effects of multiple confounding factors. Although receiver operator curve (ROC) analysis indicated that EMT has a limited value to be used as an indicator of the pregnancy rate as evidenced by the area under the curve (AUC) of 0.59 (95% CI= 0.53, 0.63), it was not possible to determine a cutoff of the endometrial thickness value with an acceptable trade-off between sensitivity and specificity Conclusion: There is a positive relationship between the EMT measured on the day of hCG injection and PR and that EMT is an independent factor. Further prospective study is needed to explore the issue in more detail in our setup.

ЭФФЕКТИВНОСТЬ МЕДИКО-ОРГАНИЗАЦИОННЫХ МЕРОПРИЯТИЙ У ЖЕНЩИН С БЕСПЛОДИЕМ ПРИ НИЗКОМ ОВАРИАЛЬНОМ РЕЗЕРВЕ

The priority direction of the health care system is to increase the birth rate. In the world, as well as in our country, there is an increase in the number of women diagnosed with infertility and having a low ovarian reserve [1]. This is partly due to the improvement in the quality of modern life and delayed pregnancy planning, the shift of childbearing to a late reproductive age. On the other hand, in young women, a low ovarian reserve occurs after ovarian surgery, infectious and inflammatory disease[2]. Clinics are actively implementing new medical and organizational approaches to improve the effectiveness of treatment of this category of women using cycles of assisted reproductive technologies with the accumulation of embryos in order to increase the cumulative incidence of clinical pregnancy, especially for the treatment of couples who do not agree to donor oocytes [3]. This paper analyzes the effectiveness of medical and organizational measures in women with infertility and low ovarian reserve [4,5].Research methods: analytical, statistical. The main group — 50 women (age 37.34 + 0.43 years) who completed cycles of embryo accumulation with genetic diagnostics; comparison group — 55 women (age 37.32 + 0.25 years) who completed cycles of embryo accumulation without genetic diagnosis. Results: the proposed medical and organizational measures can significantly increase the pregnancy rate and are recommended for implementation.

Chronic endometritis: A protracted discussion

Introduction Chronic endometritis is one of the most important factors leading to reduced fertility in women. The protracted discussion about the presence of this nosology in clinical practice for more than 100 years does not allow to establish the true frequency of chronic endometritis in women of reproductive age. At the present stage, due to the unfavorable demographic situation both in the Russian Federation and in many countries, the study of chronic endometritis, as one of the main determinants of the lesions of the morphological and functional state of the endometrium, is relevant.The purpose of the study is to determine the current state of the problem of verification of chronic endometritis in women with infertility, reproductive losses and repeated failure of assisted reproductive technologies (ART).Materials and methods The sources of information were publications from the databases PubMed, Google Scholar, elibrary.ru and Russian medical journals in the field of obstetrics and gynecology, as well as pathological anatomy in the period from 2013 to 2022.Results and discussion An analysis of the literature showed that chronic endometritis is the cause of infertility, miscarriage and ineffective ART protocols and leads to decrease of the regenerative potential and endometrial reserve. Despite the evidence of the negative impact of chronic endometritis on the reproductive function, at the present stage, the discussion regarding diagnostic approaches to this nosology continues. The use of the histological method of research, as the main and available method for diagnosing the state of the endometrium, is not always allow to verify chronic endometritis, which dictates the need of using high technological methods to confirm and clarify the severity of the pathological process.Conclusion A unified algorithm for diagnosing chronic endometritis in patients with infertility, miscarriage, ineffective ART cycles and a qualified approach to the morphological diagnosis of the state of the endometrium, standardization of the diagnosis of chronic endometritis, and competent interpretation of immunohistochemical data make it possible to select a pathogenetically substantiated therapy aimed at the rehabilitation of reproductive function.

Impact of thyroid autoimmunity on pregnancy outcomes in euthyroid women following fresh/frozen-thawed embryo transfer.

To investigate whether thyroid autoimmunity (TAI) is associated with assisted reproductive technology (ART) outcomes in euthyroid women undergoing fresh embryo transfer (ET) and frozen-thawed embryo transfer (FET). A retrospective cohort study. Pregnancy and neonatal outcome after freshETor FETwere compared between the positive and negative thyroid autoimmune antibody groups. A total of 5439 euthyroid women who started their ART cycle at our centre between 2015 and 2019 were included. The thyroid antibody positive group had a greater mean age than the thyroid antibody negative group (32(29,35) vs. 31(28,34), p < .001). Women with positive thyroid antibody presented with a higher prevalence of diminished ovarian reserve (DOR) (9.1% vs. 7.1%, p = .026) and lower number of oocyte retrieved (9(5,15) vs. 10(6,15), p = .020), but difference was not significant after adjusting for age. The pregnancy rate, live birth rate, pregnancy loss rate, preterm delivery rate and low birthweight rate between the thyroid antibody positive and thyroid antibody negative groups were comparable both in fresh ET cycles and FET cycles. Subanalysis of the treatment outcomes when using a stricter threshold of TSH of 2.5 mIU/L showed no difference to that achieved when using an upper limit of 4.78 mIU/L. The present study reveals that patients with anti-thyroid peroxidase antibodies (TPOAbs) and/or antithyroglobulin antibodies (TgAbs) showed no significant differences in pregnancy outcomes following fresh ET and FET when compared with patients with negative thyroid antibodies.

ART outcomes of patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China

BackgroundIsolated Hypogonadotropic Hypogonadism (IHH) is a rare reproductive disorder caused by the dysfunction of the gonadotropin-releasing hormone axis. Patients with IHH typically fail to enter or develop through puberty and retain infertile without an exogenous hormone supplement. This study aimed to investigate the population characteristics and reproductive outcomes in IHH patients undergoing assisted reproductive technology (ART) treatment, and evaluate the best-performed predictor for ovarian response and clinical pregnancy in patients with IHH.MethodsThis retrospective cohort study included 83 women with IHH who underwent fresh ART cycles and non-diagnosed controls (n = 676). The receiver operating characteristic curves were generated to assess the predictor for the ovarian response. Logistic regression analyses were performed to investigate the independent factors for clinical pregnancy in IHH.ResultsThe basal hormone levels were significantly lower in the IHH group compared to the control group. The fertilization rate and 2PN rate were significantly higher in IHH groups, as was the number of transferable embryos. The study identified that AMH was the best predictor of high ovarian response in IHH, with an AUC of 0.767 (0.573, 0.961). Conversely, the follicle-to-oocyte index (FOI) exhibited the highest AUC of 0.814 (0.642, 0.985) for predicting low ovarian response. Based on FOI values, the IHH patients were divided into two groups, and the study found a significant increase in clinical pregnancy rate (43.8%, 58%; P < 0.001) and live birth rate (37.5%, 58%; P < 0.001) from the low FOI to the normal FOI groups. Moreover, the number of oocytes retrieved, fertilized embryos/rate, 2PN embryos/rate, and number of excellent quality embryos were significantly higher in the normal FOI group (P < 0.001 or P = 0.005) than in the low FOI group. Logistic regression analyses revealed FOI to be the independent factor affecting clinical pregnancy in IHH patients.ConclusionsThe study findings suggest that patients with IHH were good responders to IVF treatment. Although AMH was the best-performed predictor for the high ovarian response, FOI had the best capability in predicting the low ovarian response. FOI was an independent factor affecting clinical pregnancy in IHH undergoing IVF/ICSI.

The status of ART in the public health sector in Africa: a multi-country survey

Research questionWhat is the current availability of treatment with assisted reproductive technology (ART) in the public sector in Africa, and what are the facilitators and barriers towards its provision? DesignCross-sectional quantitative and qualitative data were collected in two phases from February 2020 to October 2021. Key informants were identified from countries known to provide ART in Africa based on data from the African Network and Registry for Assisted Reproductive Technology and the 2019 Surveillance from the International Federation of Fertility Societies. Quantitative data were collected via a structured questionnaire (Phase 1); public centre-specific quantitative and qualitative data were then collected via a semi-structured questionnaire followed by a virtual interview (Phase 2). Data were analysed descriptively. ResultsInformants from 18 countries reported the existence of 185 ART centres in 16 countries. Twenty-four centres (13.0%) in 10 of 16 countries (62.5%) were public. The majority of public centres (20/22 [90.9%]) reporting on ART performed <500 ART cycles per annum. Although public institutions covered most of the cost for ART, copayments from patients were universally required. The number of ART cycles per annum was inversely correlated to the copayment. Lack of policy and legislation, high costs and bureaucratic obstacles were identified by participants as the leading challenges in the delivery of public service ART. ConclusionLack of public ART services leads to chronic and profound health inequities. Enablers of public service ART in the region are the same known to support ART services in general, namely policy and legislation, appropriate funding and good health service infrastructure. Addressing these requires the collated efforts of many stakeholders.

Effects of uterine polyps on embryo implantation in IVF cycles

Embryo implantation requires healthy uterine endometrium for natural or assisted reproductive technology conception. However, in presence of any endometrial anatomical abnormality or disease, implantation is affected. Uterine or endometrial polyps are over growths of endometrial cells that extend into the uterine cavity. They are usually noncancerous. There can be one or many polyps. They range in size from a few millimeters to several centimeters or larger. They may cause vaginal bleeding in between periods, heavy periods, frequent or unpredictable periods and infertility. The objective of this study was to find out effects of endometrial polyps on embryo implantation in assisted reproductive technology cycles of Saudi women being treated at an infertility clinic. This was a case-control study. The participants were in ratio of 5:1 i.e., for every 5 patients there was one control. The polyp diagnosis was carried out with ultrasound and endometrial biopsy. We observed high incidence of implantation failure in patients with uterine polyps as compared to that in the control patients. The results of this study indicated that the presence of endometrial polyps is a risk factor for infertility and failure of conception after in vitro fertilization.

The Predictive Value of Serum ß-HCG Levels in The Detection of Ectopic Pregnancy Sixteen Days after Embryo Transfer: A Cross-Sectional Study.

To detect the predictive value of beta human chorionic gonadotropin (β-hCG) levels 16 days post embryo transfer (ET) regarding detection of an ectopic pregnancy (EP) in assisted reproductive technology (ART) cycles. In this cross-sectional study, we reviewed the database of Royan Institute from January 2011 to December 2014 and from January 2017 to December 2019 retrospectively. All cases with positive β-hCG levels sixteen days after ET were screened (n=4149). The pregnancies with oocyte or embryo donation and the multiple pregnancies based on the first ultrasound were excluded. All eligible singleton pregnancies with documented serum β-hCG levels at Royan institute laboratory (n=765) were included and then classified according to the type of pregnancy: EP (n=189) or non-EP (n=576). The data of the treatment cycle was extracted from the patients' files. A receiver operating characteristic (ROC) curve was used to detect the predictive power of the first measurement of β-hCG level in distinguishing EP from ongoing pregnancy in the ART and intrauterine insemination (IUI) cycles separately. Sensitivity, specificity, area under the ROC curve and 95% confidence intervals (CI) were calculated for each of the estimates. The mean levels of β-hCG 16 days after ET were remarkably higher in the ongoing pregnancy group than the EP group (1592.35 ± 87 IU/L vs. 369.69 ± 50.61 IU/L, P<0.001). The β-hCG thresholds predictive of ongoing pregnancy were 278 IU/L as the most suitable cut-off to predict viable pregnancy with a sensitivity of 72.8%, a specificity of 67.5%, a positive predictive value of 77.8%, standard error of 0.02, and a confidence interval of 73.8- 81.7%. However, this relationship was not found in IUI cycles. Based on these findings, if β-hCG levels 16 days after ET are below 278 IU/l, close follow-up is recommended, until either the diagnosis of EP or miscarriage is established.

MP43-14 THE IMPACT OF VARICOCELE EMBOLISATION ON SPERM DNA FRAGMENTATION &amp; ASSISTED REPRODUCTIVE TECHNOLOGY (ART) OUTCOMES

You have accessJournal of UrologyCME1 Apr 2023MP43-14 THE IMPACT OF VARICOCELE EMBOLISATION ON SPERM DNA FRAGMENTATION & ASSISTED REPRODUCTIVE TECHNOLOGY (ART) OUTCOMES Adwoa Nyantakyi, Sheena Lewis, Yau Thum, Timothy Bracewell-Milnes, James Nicopoullos, Mohamed Al-Hussini, Jonathan Ramsay, Suks Minhas, and Tet Yap Adwoa NyantakyiAdwoa Nyantakyi More articles by this author , Sheena LewisSheena Lewis More articles by this author , Yau ThumYau Thum More articles by this author , Timothy Bracewell-MilnesTimothy Bracewell-Milnes More articles by this author , James NicopoullosJames Nicopoullos More articles by this author , Mohamed Al-HussiniMohamed Al-Hussini More articles by this author , Jonathan RamsayJonathan Ramsay More articles by this author , Suks MinhasSuks Minhas More articles by this author , and Tet YapTet Yap More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A varicocele is a common and treatable cause of male infertility. Current guidelines advocate for treatment of varicoceles based on abnormal semenalysis rather than abnormal sperm DNA fragmentation (SDF). High SDF has been associated with poor pregnancy outcomes following ART. The aim of the study was to determine the outcomes of varicocele embolisation in an infertile male population on SDF and subsequent ART outcomes. METHODS: A retrospective study of 130 consecutive male partners of infertile couples with a clinical varicocele between 2015 and 2022 were included. 119 of these men underwent varicocele embolisation by a team of 2 radiologists, whilst 11 declined. SDF was assessed by the alkaline Comet test pre-intervention and at least 3 months after. 84 treated and the 11 untreated men proceeded to ICSI. Baseline couple parameters such as age, and pregnancy and live birth rate outcomes in the ART cycle following this intervention between groups were analysed. T & chi-square tests were used on continuous and categorical data respectively (significance rate p<0.01). RESULTS: Varicocele embolisation significantly reduced the proportion of sperm with DNA damage across all three Comet parameters (p<0.01) (Table 1). Only 18% of these men had normal semenalysis. Baseline parameters for men and women were similar with an average male age of 39 and female age of 37 for both groups. Couples who underwent embolisation had a significantly better pregnancy rate (65% vs 18%, p<0.01) and higher live birth rate which did not reach significance due to low numbers (32% vs 9%, p=0.11). CONCLUSIONS: There was a significant reduction in SDF following varicocele embolisation in this population of men of couples with infertility, with a significant difference in pregnancy rate outcomes in the treated group. Repair of clinical varicoceles improves sperm DNA quality, and can optimize fertility treatment success, even in patient with normal semenalysis. Limitations of the study include small numbers in the ‘untreated’ arm and lack of randomisation, a future avenue for research. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e606 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adwoa Nyantakyi More articles by this author Sheena Lewis More articles by this author Yau Thum More articles by this author Timothy Bracewell-Milnes More articles by this author James Nicopoullos More articles by this author Mohamed Al-Hussini More articles by this author Jonathan Ramsay More articles by this author Suks Minhas More articles by this author Tet Yap More articles by this author Expand All Advertisement PDF downloadLoading ...

The influence of reproductively significant autoantibodies determined in the follicular fluid on the quality of the obtained oocytes and embryos, as well as on the implantation rate in assisted reproductive technology cycles

BACKGROUND: According to reports, the efficiency of in vitro fertilization and intra cytoplasmic sperm injection protocols is decreased in patients positive for various autoantibodies, as opposed to autoantibody negative patients. However, there are contradictory data indicating no autoantibody effect on the outcome of infertility treatment using assisted reproductive technology.&#x0D; AIM: The aim of this study was to evaluate the embryological outcome and clinical efficiency of infertility treatment in in vitro fertilization and intra cytoplasmic sperm injection protocols in women in the presence of reproductively significant autoantibodies.&#x0D; MATERIALS AND METHODS: This prospective study enrolled 90 infertile patients undergoing assisted reproductive technology treatment. The follicular fluid obtained on the day of oocyte retrieval was evaluated for a wide autoantibody panel using commercial ELISA kits. The main group (n = 52) included women with autoantibody levels determined in the follicular fluid of more than three standard deviations from the mean values determined among all patients. The comparison group consisted of 38 women with autoantibody levels of less than three standard deviations from all subjects. The intergroup comparative analysis included clinical and anamnestic data, hormonal parameters, ovarian reserve, embryological data, and in vitro fertilization and intra cytoplasmic sperm injection efficiency.&#x0D; RESULTS: Reliably lower ovarian reserve parameters (anti-Mullerian hormone levels 1.9 (1.4; 4.0) vs. 3.3 (2.2; 6.5) ng/ml; p = 0.005; number of antral follicles 8.5 (6.0; 12.0) vs. 11.0 (9.0; 17.0); p = 0.003) have been noted in the main group relatively to the comparison group. The autoantibodies to thyroid peroxidase and cardiolipin content in the follicular fluid has been shown to be negatively associated with the number of two-pronuclear zygotes, the presence of autoantibodies to aromatase correlating negatively with the fertilization rate. Furthermore, the follicular fluid levels of autoantibodies to thyroid peroxidase (105 IU/ml) and cardiolipin (5.1 IU/ml) are reliably associated with a higher frequency of a suboptimal response to previous controlled ovarian stimulation, a lower incidence of high quality embryos on days 3 and 4 of in vitro cultivation, a decreased number of top-quality blastocysts, and the clinical efficiency of in vitro fertilization and intra cytoplasmic sperm injection programs.&#x0D; CONCLUSIONS: The presence of reproductively significant autoantibodies is an independent risk factor for reducing the total efficiency of assisted reproductive technology treatment.

Зміни в гемокоагуляційній системі після прегравідарної підготовки перед програмою ДРТ у вагітних з інфекціями, що передаються статевим шляхом, в анамнезі

Purpose - to analyze the dynamics of laboratory parameters of haemocoagulation system functioning after pregravid preparation before assisted reproductive technologies (ART) cycles in pregnant women with a history of sexually transmitted infections (STIs). Materials and methods. The functioning of the haemocoagulation system after the ART program in women with infertility and a history of STIs was analyzed: the Group 1 - 56 pregnant women received the treatment and preventive measures proposed by us in the pregravid period; the Group 2 - 55 pregnant women received conventional treatment and preventive measures. The state of the hemostasis system was assessed by the following indicators: fibrinogen concentration, activated recalcification time, activated partial thromboplastin time (APTT), integrative «index of thrombodynamic potential» (ITP), concentration of fibrin and fibrinogen degradation products (FDP) and the level of more stable but less biologically active metabolites of prostacyclin (6-keto-PGF1α) and thromboxane (T×B2). The statistical processing of the study results was performed using standard software «Microsoft Excel 5.0» and «Statistica 8.0». Results. During the period of final formation of the placental barrier in pregnant women of the Group 1, the APTT slowly lengthened (31.3±1.6 s - in the trimester ІІ; 34.3±2.9 s - in the trimester III) with increasing gestational age and significantly differed from the indicators in the Group 2 (27.6±3.0 s and 30.2±1.7 s, respectively; p&lt;0.05); activated recalcification time slowly decreased during the trimesters II and III of gestation in pregnant women of the Group 1 (63.1±2.8 s and 59.3±2.8 s, respectively); gradually decreased the level of FDP (5.8±0.27×10-2 g/l and 5.1±0.22×10-2 g/l), in contrast to the level of FDP in the Group 2, in which this indicator gradually increased (9.4±0.17×10-2 g/l and 11.6±0.27×10-2 g/l); (p&lt;0.01). The level of stable T×B2 in the trimester II decreased by 2 times and was lower (p&lt;0.05) than in the Group 2; the level of stable 6-keto-PGF1α increased in the trimester III (p&lt;0.05). This resulted in an increase in the PgI2/T×A2 balance in the Group 1 from 0.34±0.02 to 1.16±0.03, which corresponded to the physiological needs of systemic and organ hemodynamics during pregnancy. Conclusions. The development and implementation of effective pregravid preparation before ART cycles in women with a history of STIs and medical correction during pregnancy contribute to the increase of the adaptive compensatory and adaptive potential of maternal haemocoagulation homeostasis and perinatal fetal care. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Novel deleterious splicing variant in HFM1 causes gametogenesis defect and recurrent implantation failure: concerning the risk of chromosomal abnormalities in embryos.

Poor ovarian response (POR) affects approximately 9% to 24% of women undergoing in vitro fertilization (IVF) cycles, resulting in fewer eggs obtained and increasing clinical cycle cancellation rates. The pathogenesis of POR is related to gene variations. Our study included a Chinese family comprising two siblings with infertility born to consanguineous parents. Poor ovarian response (POR) was identified in the female patient who had multiple embryo implantation failures occurring in subsequent assisted reproductive technology cycles. Meanwhile, the male patient was diagnosed with non-obstructive azoospermia (NOA). Whole-exome sequencing and rigorous bioinformatics analyses were conducted to identify the underlying genetic causes. Moreover, the pathogenicity of the identified splicing variant was assessed using a minigene assay in vitro. The remaining poor-quality blastocyst and abortion tissues from the female patient were detected for copy number variations. We identified a novel homozygous splicing variant in HFM1 (NM_001017975.6: c.1730-1G > T) in two siblings. Apart from NOA and POI, biallelic variants in HFM1 were also associated with recurrent implantation failure (RIF). Additionally, we demonstrated that splicing variants caused abnormal alternative splicing of HFM1. Using copy number variation sequencing, we found that the embryos of the female patients had either euploidy or aneuploidy; however, both harbored chromosomal microduplications of maternal origin. Our results reveal the different effects of HFM1 on reproductive injury in males and females, extend the phenotypic and mutational spectrum of HFM1, and show the potential risk of chromosomal abnormalities under the RIF phenotype. Moreover, our study provides new diagnostic markers for the genetic counseling of POR patients.

Changes in the immune system in pregnant women, after pre­gravid preparation before the DRT program, with a history of sexually transmitted infections

The objective: to analyze the dynamics of laboratory indicators of the functioning of the immune system in pregnant women with a history of sexually transmitted infections (STIs) before and after pre-gravid preparation before cycles of assisted reproductive technologies (ART). Materials and methods. An analysis of the functioning of the immune system was carried out in 247 women with infertility who had a history of STIs and planned to participate in the DRT program: 115 women underwent our proposed pre-gravid training, of which 56 women in the DRT program ended in pregnancy, who entered the 1st group and received the proposed we take medical and preventive measures; 132 women underwent standard pre-gravid training, of which 55 women in the DRT program ended in pregnancy, who were included in the II group and received generally accepted medical and preventive measures. An in-depth immunological examination included: the absolute number of blood leukocytes and lymphocytes, as well as their subpopulations: CD3+ CD4+ helpers; CD3+ CD8+ cytotoxic T cells; activated CD3+DR+ T-lymphocytes; B-lymphocytes CD19+; (natural killers) of CD16+, CD56+, CD50+ cells. Statistical processing of research results was carried out using standard programs «Microsoft Excel 5.0» and «Statistica 8.0». Results. During immunological control before the start of preparation for DRT, immune maladaptation was observed in both study groups and there were no reliable changes in immunological indicators. During pregnancy, in the group of patients who received our proposed pre-gravid preparation, a probable decrease (p&lt;0.05) of the immunoregulatory coefficient from 2.17 to 1.87 was observed, as a result of adequate correction of derived immunological disorders, compared to pregnant women of the II group (2,20–2.19). As a result of the pregravid preparation offered by us, in 84,3% of the patients of the I group, stimulation of the cellular link of immunity was observed, the phagocytic activity of neutrophils and the number of B-lymphocytes increased, the number of M-immunoglobulins decreased by 267.3±14.2 mg% versus 257.7±12, 7 mg%, p&lt;0.05 Conclusions. The development and implementation of effective pre-gravid preparation before DRT cycles in women with a history of STIs and medical correction during pregnancy contributes to increasing the adaptive compensatory-adaptive potential in the immune homeostasis of the mother and perinatal protection of the fetus.

Financial costs of assisted reproductive technology for patients in low- and middle-income countries: a systematic review.

What are the direct costs of assisted reproductive technology (ART), and how affordable is it for patients in low- and middle-income countries (LMICS)? Direct medical costs paid by patients for infertility treatment are significantly higher than annual average income and GDP per capita, pointing to unaffordability and the risk of catastrophic expenditure for those in need. Infertility treatment is largely inaccessible to many people in LMICs. Our analysis shows that no study in LMICs has previously compared ART medical costs across countries in international dollar terms (US$PPP) or correlated the medical costs with economic indicators, financing mechanisms, and policy regulations. Previous systematic reviews on costs have been limited to high-income countries while those in LMICs have only focussed on descriptive analyses of these costs. Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA), we searched PubMed, Web of Science, Cumulative Index of Nursing and Allied Health Literature, EconLit, PsycINFO, Latin American & Caribbean Health Sciences Literature, and grey literature for studies published in all languages from LMICs between 2001 and 2020. The primary outcome of interest was direct medical costs paid by patients for one ART cycle. To gauge ART affordability, direct medical costs were correlated with the GDP per capita or average income of respective countries. ART regulations and public financing mechanisms were analyzed to provide information on the healthcare contexts in the countries. The quality of included studies was assessed using the Integrated Quality Criteria for Review of Multiple Study designs. Of the 4062 studies identified, 26 studies from 17 countries met the inclusion criteria. There were wide disparities across countries in the direct medical costs paid by patients for ART ranging from USD2109 to USD18592. Relative ART costs and GDP per capita showed a negative correlation, with the costs in Africa and South-East Asia being on average up to 200% of the GDP per capita. Lower relative costs in the Americas and the Eastern Mediterranean regions were associated with the presence of ART regulations and government financing mechanisms. Several included studies were not primarily designed to examine the cost of ART and thus lacked comprehensive details of the costs. However, a sensitivity analysis showed that exclusion of studies with below the minimum quality score did not change the conclusions on the outcome of interest. Governments in LMICs should devise appropriate ART regulatory policies and implement effective mechanisms for public financing of fertility care to improve equity in access. The findings of this review should inform advocacy for ART regulatory frameworks in LMICs and the integration of infertility treatment as an essential service under universal health coverage. This work received funding from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO). The authors declare no competing interests. This review is registered with PROSPERO, CRD42020199312.

Low anti-mullerian hormone decreased clinical pregnancy and increased risk of poor ovarian response in women over 35 years of age.

Low anti-mullerian hormone decreased clinical pregnancy and increased risk of poor ovarian response in women over 35 years of age.

Controlled ovarian stimulation for endometriosis patients with ultra-long GnRH-agonist or GnRH-antagonist protocols: A retrospective study by propensity score matching.

Although in vitro fertilization with embryo transfer is the most effective treatment for infertile patients with endometriosis, ovarian stimulation protocols are controversial. We recruited 639 patients with endometriosis from January 2016 to June 2020; 111 and 528 patients were treated with the gonadotropin-releasing hormone (GnRH) antagonist and ultra-long GnRH agonist protocols, respectively. Potential baseline differences between the regimens were adjusted by propensity score matching. Clinical and laboratory data, including the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR), were compared. Ovulation induction required significantly longer use of gonadotropins in the GnRH agonist group. However, the GnRH agonist group had a lower starting dose of gonadotropin (all p < 0.05). Furthermore, significantly lower clinical pregnancy, implantation, and live birth rates were observed in the GnRH antagonist group receiving fresh assisted reproductive technology cycles (all p < 0.05); however, pregnancy outcomes using the subsequent freeze-thaw cycles for the same oocyte retrieval were not significantly different. CCPR and CLBR for the oocyte retrieval cycles of the antagonist and ultra-long agonist protocols were similar. The ultra-long agonist protocol resulted in more favorable implantation of fresh embryos and improved clinical outcomes of the fresh cycle. This novel strategy could be appropriate for endometriosis patients who are temporarily unsuitable for fresh embryo transfer. The GnRH antagonist protocol can be combined with the whole embryo freezing strategy to achieve CCPR and CLBR similar to the ultra-long agonist regimen, thus simultaneously avoiding the long pre-treatment duration of GnRH agonists during the ultra-long agonist protocol.

The average gonadotrophin dosage per follicle is predictive of ovarian response and cumulative live birth chances after in vitro fertilization: a retrospective cohort study

BackgroundWith the development of assisted reproduction technology (ART), many indicators have been proposed to evaluate ovarian response, and then predict pregnancy outcomes. In general, the predictive values remain limited.ObjectiveTo further explore the indicators to evaluate ovarian sensitivity to gonadotrophin (Gn) stimulation more accurately.MethodsThis retrospective cohort study included 330 women who underwent an entire ART cycle. We aimed to assess whether a new index, termed as average Gn dosage per follicle, could be used as a marker for ovarian response and pregnancy outcomes. It was calculated as the ratio of total Gn dose during ovarian stimulation and the number of pre-ovulatory follicles (PFC) on the trigger day. Patients were divided into three subgroups according to the average Gn dosage per follicle: below the 33rd percentile (Group A), between 33rd and 67th percentiles (Group B), and above the 67th percentile (Group C). Then stimulation data, laboratory and clinical outcomes were compared among the groups.ResultsThe results showed patients in Group A had the best ovarian response, the number of retrieved oocytes was significantly higher than in Group B and C. A multivariate regression analysis showed that average Gn dosage per follicle was an independent predictor of cumulative live birth rates (CLBRs) [adjusted odds ratio (OR): 0.96, 95% confidence interval (CI): 0.95–0.98, P < 0.01].ConclusionsThe present study showed that average Gn dosage per follicle appears to be a highly reliable index of ovarian response to exogenous Gn and can be useful to estimate CLBR.

Outcome analysis of ICSI assisted pregnancy using testicular sperm versus ejaculated sperm in man with severe oligozoospermia in the same ART cycle: A case report.

Intracytoplasmic sperm injection (ICSI) has become the most common method for couples with male factor infertility, and source of sperm for the procedure have evolved over time. but few have examined testicular sperm extraction vs. ejaculated sperm use for severe oligozoospermia in the same assisted reproductive technology (ART) cycle. Here, we evaluated the clinical outcomes after ICSI with testicular sperm or ejaculated in man with severe oligozoospermia in the same ART cycle. A couple who had failed the first ART cycle with ejaculated sperm, using the freshly ejaculated sperm and testicular sperm for ICSI during the second ART cycle by lack of enough sperm to fertilize in an ICSI attempt. The patient was diagnosed with severe oligozoospermia, and routine semen analysis revealed sperm concentration is less than 2 million/mL. The patient using testicular sperm versus ejaculated sperm with ICSI assisted pregnancy in the same ART cycle. We found that superior cleavage rate, number of embryos transferred and blastocyst rate with the use of testicular rather than ejaculated sperm-ICSI in the couple. The results described here suggest that use of testicular sperm may improve biologic outcomes, especially for couples with male-partner oligozoospermia who previous ICSI failures. Our case report supported the efficacy of testicular sperm preference over ejaculated sperm for ICSI in men with severe male factor infertility. It is a paradigm shift concerning the use of ejaculated sperm as the preferable source of sperm for ICSI, add to the small amount of literature on testicular sperm extraction vs. ejaculated sperm use for severe oligozoospermia in the same ART cycle.

The Impact of Chronic Endometritis on Infertility: Prevalence, Reproductive Outcomes, and the Role of Hysteroscopy as a Screening Tool

Objectives: The objective of this study was to examine the prevalence of chronic endometritis (CE) in infertile women, its impact on reproductive outcomes, and the accuracy of hysteroscopy as a screening tool for CE. Design: This was a prospective observational study. Participants: Participants involved in this study were 514 asymptomatic patients with infertility. Setting: The review was conducted in a tertiary care center. Methods: The participants underwent a hysteroscopy and endometrial biopsy (EMB). Antibiotics were given for cases of CE. We investigated the prevalence of CE in patients starting assisted reproductive technologies (ART) as a primary outcome. Secondary outcomes were the clinical pregnancy rate (CPR) in the ART cycle after hysteroscopy, EMB, and antibiotic treatment in cases of CE; the cumulative CPR in the subsequent 2 years after hysteroscopy and EMB; the sensitivity and specificity of hysteroscopy as a screening tool compared to EMB as the “gold standard” for diagnosing CE. Results: CE was identified in 2.8% of patients starting ART (11/393). CPRs did not differ significantly between patients with CE and the entire cohort of patients without CE in the subsequent ART cycle (OR: 0.43; 95% CI: 0.09–2.02) or in the 2 years after EMB (OR: 0.56; 95% CI: 0.16–1.97). In a matched control comparison (with matching for age, basal FSH, and cause of infertility), CPR in patients with CE did not differ in the subsequent ART cycle (OR: 0.39; 95% CI: 0.09–1.61); however, their CPR in the 2 years after EMB was significantly lower (OR: 0.22; 95% CI: 0.13–0.38). The sensitivity and specificity of hysteroscopy as a screening tool for diagnosing CE were 8.3% and 90.1%, respectively. Limitations: Due to our cohort’s low CE prevalence, we could not detect significant differences in CPRs. Conclusion: CE is rare in our studied population of asymptomatic patients starting ART. Hysteroscopy cannot replace EMB for diagnosing CE.