Type Of Infertility Research Articles

Frequency Of Endometriosis in Females with Infertility Undergoing Diagnostic Laparoscopy

Endometriosis is the most common, chronic condition. Although some females are asymptomatic, the majority of women come with infertility, adnexal mass, or pelvic pain. Endometriosis treatment in the context of infertility poses a variety of challenging clinical issues. Objective: The objective of current study is to identify frequency of endometriosis on laparoscopy in females with infertility. Methods: This retrospective study was done at the Department of Obstetrics and Gynaecology, Saint Luke's General Hospital, Kilkenny, Ireland. Medical records of 215 females meeting the inclusion criteria underwent diagnostic laparoscopy were included. Basic demographical details and clinical examination was evaluated and presented through descriptive statistics. On diagnostic laparoscopy, representative sample was taken and sent to hospital histopathology for evaluation of endometriosis. Chi square test was applied to identify the influence of variables on endometriosis. Results: Mean age of females was 28.67 ± 6.35 years. Mean duration of marriage was 6.63 ± 5.26 years. There were 80 (37.21%) women in which endometriosis was diagnosed. No significant statistical association was seen for endometriosis with age, infertility type and duration of infertility. Conclusions: The findings of this study show an increasing trend in endometriosis identification or occurrence in women with infertility. Endometriosis with infertility is not an uncommon disease in women. Though laparoscopy is intrusive method, but with the right training the issues and complications that come with it can be reduced, which benefits the patients and offers us a clear picture or pathology of the disease

Is Endometrial Receptivity Assay (ERA) Useful in Patients with Repeated Implantation Failure Undergoing Single, Autologous Euploid Embryo Transfer?

Background: Our aim in this study was to evaluate whether endometrial receptivity assay (ERA) test improves single, autologous euploid frozen-thawed embryo transfer (FET) outcomes in patients with repeated implantation failure. Methods: This was a retrospective cohort study which was conducted in a University affiliated private hospital. The study included 135 patients with repeated implantation failure who underwent single, autologous euploid ERA adjusted and non-adjusted FET. Patients were stratified into three groups, patients with receptive endometrium based on the ERA test, patients with non-receptive endometrium based on the ERA test and patients who did not receive the ERA test (control group). The three groups were compared in terms of FET outcomes. Results: Of 135 patients, 73 had the ERA test results available and 62 did not have the ERA test. Of 73 patients, 28 had non-receptive endometrium and 45 had receptive endometrium. The three groups are all the same in terms of age, body mass index, type of infertility, duration of infertility, number of previously embryo transfers and infertility causes (p > 0.05). Live birth rates were 46%, 50% and 51% for receptive, non-receptive and control groups, respectively (p > 0.05). Implantation and clinical pregnancy rates were similar between the groups, as well. Conclusions: Adjusting the embryo transfer day according to the ERA test results seems to improve FET outcomes in patients with repeated implantation failure.

Reproductive outcomes of infertile couples undergoing assisted reproductive technology who are carriers of chromosomal abnormalities: a retrospective cohort study

Background The aim of this study is to determine whether infertile couples who are carriers of chromosomal abnormalities have distinct cumulative clinical pregnancy and cumulative live birth rates among patients undergoing assisted reproductive technology (ART). Methods Design: A retrospective cohort study. Setting: Department of Reproduction and Infertility in Chengdu Women’s and Children’s Central Hospital. Patients A total of 112 couples were in the exposed group with chromosomal abnormalities, and 226 couples without chromosomal abnormalities were in the control group, totalling 338 cases enrolled from 1 January 2017 to 31 December 2020. The control group (infertile couples without chromosomal abnormalities) was 1:2 matched by female age, type of infertility (primary, secondary), and type of ART (IVF, ICSI, or IUI). The primary outcomes were cumulative clinical pregnancy rate and cumulative live birth rate. Results The results indicated that chromosome abnormalities did not lead to significant differences in primary outcomes. The overall cumulative clinical pregnancy rate and cumulative live birth rate were not statistically different between the two groups (74.8% vs. 81.6%, p = .150) and (65.4% vs. 69.1%, p = .508). Further analysis revealed that there was also no significant difference in cumulative miscarriage rate between the two groups (13.9% vs. 20.3%, p = .213). Conclusions There were no significant differences in the cumulative clinical pregnancy rate or cumulative live birth rate between infertile couples with or without chromosomal abnormalities. KEY MESSAGES The prevalence of infertility is rising year by year worldwide. Carriers of chromosomal abnormalities undergoing ART have the similar cumulative clinical pregnancy rate or cumulative live birth rate. The data we analysed have a certain significance for clinical decision-making involving ART for couples with chromosomal abnormalities, and it provides a meaningful reference for patients and physicians in the selection of PGT.

Endometrial polyps and their insinuation in the pregnancy rates of patients undergoing ICSI-FET cycles: A retrospective cohort study

To study the effect of endometrial polyps in infertility patients and their insinuation in pregnancy rates in patients undergoing ICSI-FET cycles following polypectomy.This is a retrospective study in 345 infertility patients attending Reproductive center of Sudha Hospital, Erode. Infertile women with endometrial polyps diagnosed by transvaginal ultrasound were subjected to hysteroscopic polypectomy. Vitrified embryo transfer was done one to three months following polypectomy and the clinical pregnancy rates were analysed. The age, body mass index, the type of infertility (primary or secondary), duration of infertility, pattern of menstruation, were precisely evaluated. An endometrial polyp based on their location inside the uterine cavity is assessed by hysteroscopy and the significance of the polyp location with pregnancy rates is evaluated.Of the 345 women who underwent hysteroscopic polypectomy 229 became pregnant and 116 women were non pregnant in ICSI-FET cycles. There is a strong positive association between endometrial polypectomy and pregnancy rate in ICSI-FET cycles. The incidence of Endometrial Polyps in pregnant and non-pregnant group was not related to the age, gravida and parity. Pregnancy rate after polypectomy based on polyp location is statistically insignificant. Multiple polyps are common compared to solitary polyp. Polyps are more common in posterior uterine wall than anterior, lateral walls and uterotubal junction.Hysteroscopic polypectomy gives promising results in infertility patients undergoing ICSI cycles prior to vitrified embryo transfer and location of polyps does not determine the pregnancy outcomes.

Candidate genes for infertility: an in-silico study based on cytogenetic analysis

BackgroundThe cause of infertility remains unclear in a significant proportion of reproductive-age couples who fail to conceive naturally. Chromosomal aberrations have been identified as one of the main genetic causes of male and female infertility. Structural chromosomal aberrations may disrupt the functioning of various genes, some of which may be important for fertility. The present study aims to identify candidate genes and putative functional interaction networks involved in male and female infertility using cytogenetic data from cultured peripheral blood lymphocytes of infertile patients.MethodsKaryotypic analyses was done in 201 infertile patients (100 males and 101 females) and 201 age and gender matched healthy controls (100 males and 101 females) after 72 h peripheral lymphocyte culturing and GTG banding, followed by bioinformatic analysis using Cytoscape v3.8.2 and Metascape.ResultsSeveral chromosomal regions with a significantly higher frequency of structural aberrations were identified in the infertile males (5q2, 10q2, and 17q2) and females (6q2, 16q2, and Xq2). Segregation of the patients based on type of infertility (primary v/s secondary infertility) led to the identification of chromosomal regions with a significantly higher frequency of structural aberrations exclusively within the infertile males (5q2, 17q2) and females (16q2) with primary infertility. Cytoscape identified two networks specific to these regions: a male specific network with 99 genes and a female specific network with 109 genes. The top enriched GO terms within the male and female infertility networks were “skeletal system morphogenesis” and “mRNA transport” respectively. PSME3, PSMD3, and CDC27 were the top 3 hub genes identified within the male infertility network. Similarly, UPF3B, IRF8, and PSMB1 were the top 3 hub genes identified with the female infertility network. Among the hub genes identified in the male- and female-specific networks, PSMB1, PSMD3, and PSME3 are functional components of the proteasome complex. These hub genes have a limited number of reports related to their respective roles in maintenance of fertility in mice model and humans and require validation in further studies.ConclusionThe candidate genes predicted in the present study can serve as targets for future research on infertility.

Subclinical hypothyroidism among infertile women at a tertiary hospital in South-West Nigeria

Overt thyroid dysfunction is an accepted cause of female infertility. Its milder form, subclinical hypothyroidism have also been implicated as a contributing factor to disturbed reproductive function. To determine the contribution of subclinical hypothyroidism (SCH) to the burden of infertility. This is a cross sectional, comparative study of One hundred and twenty women with primary or secondaryinfertility who presented for evaluation at gynaecological clinic and controls which are clients that came to access Family planning services. The prevalence of infertility among gynaecological patients seen in the clinic was 38.8% (192/495). The prevalence of SCH among the studied infertile women was 11.7% (7/60) compared with 3.3% (2/60) of the control group (p=0.222). The commonest type of infertility was secondary, 76.7% (46/60). All thestudied infertile women with SCH presented with secondary infertility. There was an observed statistically significant difference in the mean serum TSH (3.19±4.38mIU /L vs 1.60±1.22mIU /L) and FT3, FT4 (0.29±0.074ng/dl vs 0.95±0.16ng/dl and 0.33±0.071ng/dl vs 1.09±0.19ng/dl respectively). Subclinical hypothyroidism was found to be higher among infertile women but this finding was not statistically significant, therefore, the routine screening for SCH among infertile women might be unnecessary.

Investigation of the Relationship between Chronic Endometritis Manifestations under Hysteroscope and CD138 Expression.

Methods This study was performed to retrospectively analyze clinical cases of 523 CE patients from January 2018 to June 2020 that were confirmed by hysteroscopy before in vitro fertilization. Based on manifestations of CE under hysteroscopy, the cases were divided into three cohorts, i.e., hyperemia cohort where the patients had diffuse endometrium hyperemia; endometrial micropolyp cohort, and endometrial stroma edema and hyperplasia cohort. Small amount of endometrial tissue was collected from the patients, and CD138 IHC examination was performed. According to the results of CD138 IHC, positive patients were given antibiotic treatment (doxycycline 100 mg BID orally for 14 days), and hysteroscopy was performed again after treatment to check the efficacy of antibiotics. Results In the comparison of overall status for all patient cohorts, infertility type, BMI, bFSH, bLH, bP, bT, PRL, AMH, and CA125 were varied markedly across all cohorts (P < 0.05), with predominant incidences of polycystic ovary syndrome (PCOS) peaking within hyperemia cohort. Incidence/diagnostic rate for CD138 within hyperemia cohort was 10.06%, which was lower than the 63.16% in micropolyp cohort and 74% in edema and hyperplasia cohort (P < 0.05). No major variation existed within CD138 across micropolyp cohort/edema and hyperplasia cohort (P > 0.05). After CD138-positive CE patients were treated with antibiotics, the effective rate (0/16) within hyperemia cohort was lower than micropolyp cohort (73.61%, 53/72) and edema and hyperplasia cohort (83.24%, 154/185) (P < 0.05). The effective rate across micropolyp cohort/edema and hyperplasia cohort was not significantly different (P > 0.05). Conclusion Cases of diffuse endometrial hyperemia under hysteroscope had the lowest positive rate of CD138, and the effect of antibiotic treatment on these patients was poor. The positive rate of CD138 in patients with endometrial micropolyps and endometrial stroma edema and hyperplasia under hysteroscope was high, and the effect of antibiotic treatment was better.

Association Between Type of Infertility and Live Birth in Couples With a Single Intrauterine Insemination Resulting in Pregnancy: A Propensity Score Matching Cohort Study.

BackgroundFew studies have described the relationship between the type of infertility and live birth in patients treated with intrauterine insemination (IUI). We focused on this issue and attempted to explore it.MethodsThis retrospective study enrolled 2,256 infertile patients who underwent their first IUI cycle and were subsequently diagnosed with a clinical pregnancy at Ji’an Women and Child Health Care Hospital between 2007 and 2018. Inductees were divided into primary infertility (1,680 patients) and secondary infertility groups (876 patients). Following 1:1 propensity score matching to obtain balanced data, the COX proportional hazards model, landmark analysis, and subgroup analysis were used to assess the association between infertility types and live birth rates. Subsequently, a sensitivity analysis was employed to evaluate the potential effect of unmeasured confounding on outcomes.ResultsOf the 1,486 patients who were identified as a matched cohort, 743 were in the primary infertility group and the remaining patients were in another group. A total of 1,143 patients had live births during 431,009 person-days of follow-up (average 290.0 days). Throughout the follow-up period, patients with secondary infertility demonstrated more live births than patients with primary infertility (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.04 to 1.30; P = .007). More details were observed in the landmark analysis. Live birth rates were similar in both groups within 316 days of follow-up (HR, 0.84; 95% CI, 0.62 to 1.14; P = .269), whereas the opposite was found between 316 days of follow-up and delivery day (HR, 1.19; 95% CI, 1.06 to 1.34; P = .004). This was also obtained in a subgroup analysis of patients younger than 35 years old and patients treated with natural cycles (NCs) and IUIs.ConclusionAmong the infertile patients who underwent a single natural or stimulated cycle followed by IUI and had later pregnancies, full-term young secondary infertility mothers (<35 years of age) had a greater chance of having viable babies than the primary infertility ones. The latter may get more benefits when undergoing ovarian stimulation and IUI rather than NC-IUI.

The Association between Female Infertility and Catalase Enzyme in Karbala Province of Iraq

DBackground: One of the most significant and overlooked conceptive medical issues in non-industrial nations is the high pace of subfertility and childlessness. There is developing proof of the conceivable function of profoundly responsive results of oxygen-related agents like catalase enzyme in female subfertility. Aim of the study: To confirm this objective, the level of catalase chemical (CAT) and its connection with certain components (age, weight record, smoking, infertility duration and type of infertility) were surveyed. Method: This case control study included 100 subfertile ladies distinguished from the fertility clinic information base in maternity clinic and private facility contrasted and 100 fertile ladies. Detailed history and assessment were done, and the blood tests were moved to the biochemical lab to examine CAT as searching compounds by enzyme-linked immunosorbent assay (ELIZA) pack. Results: The catalase levels of infertile women show a significant decrease (p&lt; 0.05) when compared with the fertile control. Its shows an insignificant negative Correlation with age, BMI and duration of subfertility(p&gt; 0.05) Conclusion: Catalase was significantly decreased in patients with subfertility, and had inverse insignificant relationship between its level and duration of subfertility increment in patients with subfertility

Detection of Sperm DNA Integrity and Some Immunological Aspects in Infertile Males

Immunoinfertility caused by anti-sperm antibodies (ASAs) represents about 10–20% of infertility among couples, which interfere with sperm motility and ability to penetrate cervical mucus, sperm-oocyte binding, fertilization, and embryo development. In addition, deoxyribonucleic acid (DNA) damages are increasingly found with infertile cases affecting male reproduction potency and progeny. This study aims to assess the semen, presence of ASAs, and DNA fragmentation index in normozoospermic patients. A total number of 116 cases with an average age of 20–51 years old, and duration of infertility at 4.70 ± 2.77 are classified into 77 and 39 primary and secondary types of infertility, respectively. Mixed agglutination reaction test was used to estimate the ASAs in semen (direct method) and in seminal plasma and blood serum (indirect method), for both immunoglobulins IgG and IgA. Acridine orange test was used to detect DNA fragmentation index. The results showed a significant difference (P &gt; 0.05) for those with a secondary type of infertility at means 24.37 and 31.48 for IgG, and 14.46 ± 1.76 and 6.86 ± 0.39 for IgA by both direct and indirect methods, respectively. The direct method showed a significant difference only for the sperm tail, while that for indirect method was in sperm mid-piece. The mean of DFI for all cases was 38.25 ± 2.08, at 41.61 ± 2.19 and 31.63 ± 4.29, for both primary and secondary cases, respectively. The percentage of ASAs revealed no significant difference with DFI, except in some parts of sperm.

P-721 Prediction model of pregnancy after intrauterine insemination: accessibility, relevance for clinical use and patient counseling

Abstract Study question The aim of this study is to develop a prognostic model for the outcome of intrauterine insemination that is useful for daily clinical practice and to develop an app Summary answer Our predictive model is able to make a good distinction between patients with a good or poor pregnancy chance What is known already IUI is a common, accessible and easily accepted method of treating infertile couples with a success rate varying largely between 5% and 70%. The factors that contribute to the successful IUI rate are numerous including the woman's age, type of infertility, the number of follicles obtained by ovarian stimulation, the estradiol concentration on the day of human chorionic gonadotrophin administration, the sperm parameters (concentration, motility), duration of infertility, endometrial thickness, the number of IUI cycles. Several studies have already tried to establish a success rate formula, but no prediction model is largely used. Study design, size, duration This retrospective cohort study has been conducted at an university level fertility clinic from Oradea, Romania. Patients eligible to participate in the study were 426 infertile couples who underwent IUI treatment between January 2015 and October 2020. Participants/materials, setting, methods The 426 couples were classified into three groups: 1. male infertility factor 2. female infertility factor (minimal/mild endometriosis, ovulation disorders, tubal disease, with a single patented Fallopian tube), 3. Unexplained infertility. All couples underwent IUI with/or without ovarian stimulation and we documented several factors: age, type of infertility, infertility duration, number of procedures, ovarian stimulation, number of follicles, endometrial thickness, ovulation induction, day of induction, associated pathology, tubal patency, post wash sperm count. Main results and the role of chance Our pregnancy rate was 10.3%, according to this the couples were divided intro two groups the negative and the positive result group. We found 4 factors to be significantly associated to a positive result: age of the partners (p-value = 0.012), infertility duration (p-value = 0.018), endometrium thickness (p-value = 0.035) and semen preprocess concentration (p-value = 0.046). We calculated a probability function for a woman to get pregnant after IUI procedure: Prob = 1/(1+e-z) Z = -3.36998 + 0.364*Endometrium (mm) – 0.04567*Female Age (years) – 0.049956*Age of partner (years)– 0.17299*Duration of infertility (years) + 0.018562*prewash count (mil) – 0.9933*A (motility) + 2.29085*B(motility)+ 0.03203*post wash count For example, a patient with a score of 1.507 will have a probability of 81.86% of becoming pregnant. Our predictive model in general has a performance that is close to 0.7 AUROC -0.687 (AUROC between 0.7-0.8 has a fair performance) with a value p-0.001 (high statistical significance, CI confidence interval - 99.9%), meaning it is able to make a good distinction between couples with a good pregnancy chance and those with a poor pregnancy chance after IUI. Limitations, reasons for caution In statistical models fertility treatment chances are never 0 or 100%, and the outcome of IUI is a subject to chance and from this point of view the trick would be in repeating the cycles. Another limitation is the small cohort sample and the fact that it needs external validation. Wider implications of the findings Developing an application program that could be used easily by the clinicians in their daily clinical practice and also by the patients in order to better understand their chances at a successful procedure of assisted human reproduction that could also mean the next step after IUI, the in vitro fertilization. Trial registration number not applicable

P-593 Low dose clomiphene citrate does not reduce implantation rates - a cohort study based on modified Natural Cycle IVF

Abstract Study question Does low dose clomiphene citrate (CC) reduce implantation and eventually pregnancy and live birth rates? Summary answer Low dose CC does not reduce implantation rate and pregnancy and live birth rates – based on the model of modified Natural Cycle IVF (NC-IVF). What is known already CC is commonly used for ovulation induction in the treatment of anovulation or idiopathic infertility. It is also added to NC-IVF cycles to mildly stimulate follicular growth and to inhibit LH surge. CC reduces endometrial thickness and affects endometrial function. Therefore it is assumed that CC negatively affects implantation and thereby reduced pregnancy and live birth per embryo. However, previous studies have shown inconsistent results as previous studies mainly calculated pregnancy rates per cycle but not implantation rate per embryo. Study design, size, duration This cohort study included embryos transferred in NC–IVF and CC-NC-IVF cycles. Women with a maximum age of 42 years were treated at a university hospital between 2011 and 2016. Clinical pregnancy rate and live birth rate per embryo transferred and miscarriage rate per amniotic sac were calculated. Participants/materials, setting, methods A daily dose of 25mg of CC starting on day 5-7 of the cycle until the day of ovulation trigger was applied. A modified mixed effect Poisson regression model was used to account for the number of cycles in the same women and the number of embryos in the same cycle to achieve rate ratios (RR). Adjustment for maternal age, parity, type of infertility, duration of subfertility and indication for IVF were made. Main results and the role of chance 499 couples underwent a total of 1043 IVF cycles, 453 NC-IVF and 590 CC-NC-IVF cycles. Baseline characteristics of both groups were not different. The additional administration of CC did neither decrease clinical pregnancy rate (aRR 1.16; 95% CI: 0.90 – 1.50)[MV1] nor live birth rate per transferred embryo (aRR 1.20; 95% CI: 0.89 – 1.62). Miscarriage rate was also not different in CC-NC-IVF compared to NC-IVF (aRR 1.05; 95%: CI 0.63 – 1.76). Limitations, reasons for caution This study does not allow to draw any conclusions regarding the effect of higher CC dosages. As randomization was not performed, some bias regarding the choice of IVF treatment cannot be completely excluded. Wider implications of the findings As this study revealed for the first time that low dose CC does not affect implantation, low does CC can be used for many different treatments. However, further studies are required to evaluate if this also applies to higher CC dosages. Trial registration number not applicable

O-057 The pregnant outcome after laparoscopy treatment for subtle distal fallopian tube abnormalities in infertile population: a prospective cohort study

Abstract Study question What is the the pregnancy outcome after laparoscopy treatment for subtle distal fallopian tube abnormalities and the factors related with natural pregnancy. Summary answer The natural pregnancy rate is 46.58% after laparoscopy and patients' age, duration time of infertility and concurrent number of abnormalities are related with natural pregnancy. What is known already Subtle distal fallopian tube abnormalities are a group of diseases that are characterized by subtle variations in tubal anatomy including fimbrial agglutination, tubal diverticula, accessory ostium, fimbrial phimosis, and accessory fallopian tube. The prevalence of subtle distal fallopian tube abnormalities is high in infertile women.This group of diseases is highly related to endometriosis, especially its early stage, and may indicate fimbrial abnormalities in endometriosis. Study design, size, duration This was a prospective cohort study conducted in the Reproductive Medicine Center of an university-affiliated teaching hospital from January 2017 to December 2018. Participants/materials, setting, methods 234 patients with subtle distal fallopian tube abnormalities were included. Laparoscopies were performed by four senior reproductive surgeons who were familiar with the diagnostic criteria and surgery treatment for subtle abnormalities. The fallopian tube abnormalities were corrected and endometriosis was treated by either electrical ablation for peritoneal lesions or endometrioma excision.The participants were followed up by phone every 12 months for pregnancy outcome until 36 months after surgery. Main results and the role of chance 167 patients conceived after surgery(clinical pregnancy rate 71.37%). 109 patients conceived naturally (natural pregnancy rate 46.58%) and 59 patients conceived after in IVF（One case conceived naturally after live birth after IVF, four cases conceived naturally twice) . The average time for natural conception after surgery is 8.36±7.47 months. 51.4% of natural pregnancy occurred within 6 months and 79.8% occurred within 12 months.Among the 109 naturally conceived patients, there were 94 cases of live birth, 13 cases of natural abortion (natural abortion rate 11.92%) and 2 cases of ectopic pregnancy (ectopic pregnancy rate 1.83%). No preterm birth, multiple pregnancy or birth defects were reported in this group.The patient age(HR = 0.917,95%CI 0.870-0.917,P=0.001), duration of infertility(HR = 0.846,95%CI 0.740-0.966,P=0.014) and concurrent number of subtle abnormalities (HR = 0.636,95%CI 0.416-0.970,P=0.036) are the factors associated with natural pregnancy. The type of subtle abnormalities, type of infertility, body mess index, concurrent endometriosis, uterine cavity abnormalities and myoma are not related with natural pregnancy. Limitations, reasons for caution Not all kinds of subtle distal abnormalities are included such as paratubal cyst is excluded from the study. Not all the patients had the test of ovarian reserve such as AMH, antral follicle count and FSH level, so we couldn’t evaluate the relationship between ovarian reserve and natural pregnancy. Wider implications of the findings This is the largest clinical study that investigated the pregnancy outcome of subtle fallopian tube abnormalities in the infertile population.Laparoscopy surgery is an effective treatment for infertility patients with subtle distal fallopian tube abnormalities, especially for the young, short duration time of infertility and ≤2 types of subtle abnormalities. Trial registration number ChiCTR2000029095

P-354 Major factors influencing the clinical pregnancy rate in the first frozen blastocyst transfer: a retrospective, single center cohort study

Abstract Study question The effect of clinical and embryological characteristics on clinical pregnancy is controversial. This study investigated factors contributing to pregnancy in the first frozen blastocysts transfer. Summary answer The number and the good quality of the blastocysts transferred, assisted hatching significantly influences clinical pregnancy rate in the first transfer. What is known already Studies have shown that blastocyst-stage transfer was more favorable than cleavage-stage transfer. The effectiveness of FET is also affected by clinical factors such as female age, body mass index (BMI), infertility duration, cause of infertility, endometrial preparation regimen. Old females are more likely to have unfavorable IVF results. On the other hand, although age primarily affects the embryo formation, it does not decide the succeed of FET Various embryological factors, including the number of blastocyst transferred, top quality embryo and cleavage-stage embryo transfer or blastocyst transfer for FET were the major factors contributing to live birth rate. Study design, size, duration Study design: A retrospective cohort study Size: 596 cycles Duration: From January 2017 to December 2019 Participants/materials, setting, methods We included all cycles that ultimately underwent the first frozen blastocyst transfer procedure. Resulting in 596 cycles. Patients were treated with the GnRH antagonist protocol. All transfers were performed on an outpatient basis using a soft embryo transfer. Embryo quality was assessed on D5 according to the Gardner classification. Logistic regression was used to calculate OR and its 95% CI in univariate and multivariate analysis, statistical significane of at least 0.100 in univariate analysis. Main results and the role of chance Among 596 patients with 596 frozen blastocyst transfers, clinical pregnancy and live birth rate was 43.3% (258/596) and 31.8% (190/596), respectively. The multiple pregnancy rate was 8.9%.There was no significant difference in patients’ characteristics between those with and without clinical pregnancy. Patients with two or more blastocysts transferred for the first transfer and those with at least one good blastocyst had a higher likelihood of having clinical pregnancy with odds ratios ranging from 1.69 (95% CI 1.22 – 2.34) to 1.82 (95% CI 1.30 – 2.55). Moreover, patients who underwent assisted hatching technique had a higher odds of having clinical pregnancy (OR = 1.40, 95% CI 1.00 – 1.97). This significance pattern remained unchanged in multivariate analysis with and without the presence of other covariates such as age, infertility duration, type of infertility and endometrial thickness. The chemical pregnancy rate of two or more blastocysts and one blastocyst transfer were 54.4% and 44.5%, respectively (OR = 1.49, 95% CI 1.08-2.06). Besides, the clinical pregnancy rate was 50.0% and 37.7%, respectively (OR = 1.65, 95% CI 1.19-2.29). Finally, the live birth rate of two or more blastocysts transfer was 36.7% compared to only 27.9% of that of one blastocyst transferred (OR = 1.50, 95%CI 1.06-2.11). Limitations, reasons for caution This study was a non-randomized, retrospective design, with a limited sample size and at a single center. In some subgroup analyses was relatively small which may limit the interpretation of the power of the study. our study only included Asian populations, mostly Vietnamese Wider implications of the findings In general, consideration should be given to the transfer of blastocyst stage embryos. Limiting the number of transferred embryos can reduce the multiple pregnancy rate. Trial registration number not applicable

P-169 Low 5% VS ultra-low 3% O2 concentration on embryo culture: Is there any difference in quality and ploidy?

Abstract Study question Can embryo culture in 3% O2 concentration improve fertilization and blastocyst formation rates, as well as euploidy rate, compared to 5% O2 embryo culture? Summary answer Ultra-low oxygen concentration (3%) does not seem to improve fertilization and euploidy rate neither embryo quality and blastocyst formation rate. What is known already Low oxygen tension (5%) during embryo culture has found to be beneficial for embryo development, when compared to atmospheric O2 tension (20%). Physiologically, oxygen tension is decreasing from ∼5% in the fallopian tube to ∼2,5% in the uterus and embryos enter the uterus on the post-compaction stage, around Day 4 of their development. Additionally, our previous study demonstrated that euploidy rate was significantly higher in 5% O2 concentration compared to 20%. Thus, the purpose of this study was to evaluate whether culture of embryos to blastocyst stage could benefit from a decrease in O2 concentration, from 5% to 3%. Study design, size, duration This retrospective study, included 176 PGT-A cycles, performed at Embryolab fertility clinic from May 2017 to November 2021. Two study groups were formed, in which oxygen tension was the only different parameter of culture conditions; the 5% O2 Group consisted of 114 PGT-A cycles resulting in 832 embryos and the 3% O2 Group with 62 PGT-A cycles including 479 embryos. Euploidy, fertilization and blastocyst formation rates were compared between the two groups. Participants/materials, setting, methods In all cycles included in the study, injected oocytes were incubated to either 3% O2 or 5% O2. The CO2 concentration was 6% in both groups. Embryos were cultured to blastocyst stage. In good quality available blastocysts (expansion: &amp;gt;3, ICM: A/B, TE: A/B according to Gardner Grading System), trophectoderm biopsy was performed on Days 5/6 and embryos were analyzed for chromosomal abnormalities. All embryos were vitrified after biopsy. Statistical analysis was performed using Mann-Whitney test. Main results and the role of chance Mean female age was similar between 5% and 3% group (37.76±4.7y vs 38.35±4.19y, p = 0.2263). Fertilization rates were similar between two groups (81.04% in 5% VS 81.77 in 3%, p = 0.9718). In 5% O2 Group, cleavage rate (98.86%) was found to be significantly higher, compared to 3% O2 Group (96.86%) (p = 0.003). Blastocyst formation rate (expressed per fertilized oocyte) was found to be significantly higher in the 5% O2 Group (76.56 in 5% VS 67.22 in 3%) (p = 0.029), as well as biopsied blastocyst rate (91.9% in 5% VS 82.29% in 3%) (p = 0.0056). Euploidy rates were found to be similar between the two groups, 26.7 in 5% Group and 26.76 in 3% Group (p = 0.9272). However, more blastocysts were available for biopsy on Days 5/6 in the 5% Group, as shown above. In the 5% Group, 101 embryotransfers have been performed, 54 with positive βHCG and 42 cycles had no euploid embryos after PGT-A. In the 3% Group, 28 embryotransfers have been performed, 18 with positive βHCG, 7 cycles are pending and 24 had no euploid embryos. This is an ongoing study and clinical outcomes remain to be reported and analyzed after the completion of data selection. Limitations, reasons for caution This is a retrospective study in which cycles from the two groups were not performed simultaneously but at different time periods. In addition, all PGT-A cycles were included in the study, regardless the type of infertility (e.g. both male and non-male factor infertility). Wider implications of the findings Based on these results, it is not recommended to decrease oxygen tension below 5% during culture, as this does not improve fertilization and euploidy rates. Nevertheless, embryo quality and blastocyst formation was found to be higher in 5% Group and this findings should be confirmed in a larger sample size. Trial registration number not applicable

O-192 Concomitant autoimmunity in endometriosis-affected women and In Vitro Fertilization (IVF) outcomes: a cohort study

Abstract Study question To evaluate whether the presence of concomitant autoimmunity in endometriosis patients may affect In Vitro Fertilization (IVF)/Intracytoplasmic Injection (ICSI) outcomes. Summary answer In ‘normo-responders’ patients autoimmunity did not affected ovarian response to gonadotrophin stimulation yet was the only significant negative predictor of cumulative pregnancy rate (CPR). What is known already In the last years, endometriosis has been redefined as a multifactorial disease with a complex pathogenesis. In this setting, a role of both innate and adaptive immune systems have been proposed in endometriosis development. The coexistence of endometriosis and autoimmunity is well-documented. Also, an increased risk of more severe stages of endometriosis in patients with autoimmunity has been recently reported. Even if autoimmunity has been associated with lower pregnancy rates and higher miscarriage rates, whether the presence of autoimmunity in endometriosis patients could act as an additive factor worsening IVF/ICSI response is still not known. Study design, size, duration Single-center, retrospective, cohort study. First IVF/ICSI cycles of endometriosis patients with or without autoimmunity carried out from 2007 to 2021 at the Fertility Unit of IRCSS San Raffaele Hospital(Milan) were included. Patients with endometriosis and concomitant autoimmunity were age-matched to endometriosis only controls. Only patients with a complete disease control following endometriosis treatment were admitted to IVF/ICSI. A total of 471 patients were enrolled. The study was conducted according to STROBE guidelines for observational studies. Participants/materials, setting, methods Endometriosis diagnosis was surgical/histopathological, yet also ovarian endometriosis at ultrasound assessment by expert operators was included. Autoimmunity was assessed by blood tests for auto-antibodies and/or rheumatological records. Stratified analysis by “expected” ovarian response at baseline according to AFC and/or AMH were performed. Expected ‘poor-responders’ were defined according to Bologna Criteria. The primary outcome was CPR. Secondary outcomes included oocytes retrieved, metaphase II(MII)oocytes and ovarian sensitivity index(OSI), the latter defined as:(number of retrieved oocytes/total gonadotrophin dose)×1000. Main results and the role of chance 113/471 cases with endometriosis and concomitant autoimmunity and 358/471 age-matched endometriosis only controls were enrolled. The mean age was 35.70±3.75 and 35.95±3.72 (p = 0.543) in cases and controls respectively. No baseline differences in endometriosis disease stage (p = 0.414), surgical treatment for endometriosis prior to IVF (p = 0.617), BMI (p = 0.866) or type of infertility (p = 0.255) were observed when comparing the two groups. In “expected normo-responders”, cases with autoimmunity had significantly higher numbers of oocytes retrieved (p = 0.007), MII oocytes (p = 0.007) and OSI index (p = 0.013) when compared to controls with endometriosis only; the CPR was 12.5% in cases vs. 17.5% in controls, thus comparable between the two groups (p = 0.143). In “expected poor-responders” no significant differences were observed neither in the number of oocytes retrieved and MII oocytes, nor in OSI index; the CPR was 12% in cases with concomitant autoimmunity compared to 7.75% in controls with endometriosis only (p = 0.256). In the generalized linear models (GLMs) of independent predictors associated with CPR, in expected ‘normo-responders’ autoimmunity was the only significant negative predictor of CPR (p = 0.004) whereas in ‘poor-responders’ only age negatively affected CPR (p = 0.001). Limitations, reasons for caution This study has a retrospective design. The interpretation of results is based on the validated yet still debated definition of poor-responders according to Bologna Criteria. Results should be interpreted with caution until replicated by future research providing multi-centric and prospective design, larger sample size and more standardized data collection. Wider implications of the findings Autoimmunity does not seem to impact neither ovarian reserve nor ovarian response to gonadotropin, as it may act a ‘competitive’ rather than ‘additive’ risk factor for infertility in endometriosis. However, in ‘normo-responders’ autoimmunity seems to reduce the chances of pregnancy following IVF/ICSI perhaps impairing endometrial receptivity and embryo implantation. Trial registration number Due to the retrospective design of the study, full IRB approval at the institution was not needed.

P-191 Differences in morphokinetic patterns and clinical outcomes between fresh and frozen oocytes; a retrospective analysis

Abstract Study question Is there a difference in morphokinetics and clinical outcomes between embryos from fresh and vitrified oocytes? Summary answer Embryos from vitrified versus fresh oocytes showed a delay at the cellular stage, but no impact on time to blastulation or clinical outcomes was evident. What is known already Oocyte vitrification has greatly impacted assisted reproduction, with the number of treatments cycles using frozen oocytes more than doubling in the UK since 2013. Studies of thawed vitrified oocytes have shown similar success rates and outcomes compared to fresh, allowing the technique to be considered safe and effective. However, vitrification and thawing subjects the oocyte to stress and osmotic changes that may be evident in alterations in the timing of their morphological events. Analysis of morphokinetic markers using time-lapse incubators was performed to investigate this. Study design, size, duration Matched cohort study. A total of 823 embryos were analysed, 414 embryos from fresh oocytes and 409 from vitrified. The embryos were from the 288 ICSI treatment cycles performed at LWC in 2019. Fresh oocytes were from women less than 35 years old undergoing fertility treatment and vitrified oocytes were from egg donors under 35. Participants/materials, setting, methods Embryos graded AA, BB, BA, AB, were selected and annotated retrospectively on the Embryoscope for the following events: pronuclei appearance (tPNa) and disappearance (tPNf), time until two (t2), four (t4) and eight cells (t8), compaction initiation (tSC), the start of blastulation (tSB) and time to expanded blastocyst (tEB). PN duration, second and third embryo cell cycle (ECC), compaction and blastulation duration were also calculated as well as differences in clinical outcomes. Main results and the role of chance Embryos derived from vitrified oocytes (EVO) were observed to have a statistically significant delay in 4/8 morphokinetic events studied: t4 (p = 0.03), t8 (p &amp;lt; 0.01), tSC (p &amp;lt; 0.01) and tSB (p = 0.01). A mean delay of 1h50min was observed when compared to embryos from fresh oocytes (EFO). ECC duration showed a statistically significant difference with a delay of 48 minutes in the vitrified group. However, compaction occurred on average just 84min faster in this group, meaning no differences were observed in the time needed to achieve a full expanded blastocyst. Regression analysis revealed a correlation between the age of the oocyte and morphokinetic timings. Oocytes from older women demonstrated slower development, with age having a statistically significant impact in the following categories: tPNa, tPNf, t2 and t4. No differences found between fresh and vitrified groups in fertilization rate (80% EFO vs 79% EVO) (p = 0.841), embryo utilization rate (60% EFO and 61% EVO) (p = 0.432), implantation rate (54% EFO vs 52% EVO) (p = 0.837) and clinical pregnancy rates (49% EFO vs 42% EVO) (p = 0.502). Limitations, reasons for caution Limitations of the present study include the retrospective analysis, small sample size and the lack of adjustment for potential contributory/confounding factors such as semen quality, body mass index (BMI), antimüllerian hormone (AMH) levels, type of ovarian stimulation or type of infertility which are known possible influencers of embryo morphokinetics. Wider implications of the findings The delay observed at the cellular stage by EVO had no impact on the time the embryos needed to achieve full expansion. While vitrification affects embryo morphokinetics, it does not seem to impact the ability of the oocyte to be fertilized, activated, or to produce a viable blastocyst and pregnancy. Trial registration number Not applicable

O-130 Reproductive outcomes of normal ovarian reserve patients after progestin-primed ovarian stimulation with chlormadinone acetate vs GnRH antagonist: A retrospective study with inverse-probability-of-treatment weighting

Abstract Study question To evaluate the effectiveness of chlormadinone acetate (CMA) for preventing premature LH surge in patients with normal ovarian reserve compared to cetrorelix. Summary answer In progestin-primed ovarian stimulation (PPOS) than GnRH antagonist (GnRH-ant), the incidence of premature LH surge was significantly lower, without significant difference in oocyte maturation rate. What is known already The GnRH-ant protocol is one of the conventional protocols which has some disadvantages including increased premature LH surge rate and cancelation rate. In recent years, the PPOS protocol has attracted attention as a new ovarian stimulation using progestin as an alternative to GnRH analog for suppressing a premature LH surge, however its efficacy is still controversial. In addition, many studies have investigated the reproductive outcomes of PPOS using medroxy-progesterone acetate or dydrogesterone; however, there are few reports of CMA, an oral progestin, which is inexpensive and widely used in Japan. Study design, size, duration This retrospective cohort study was performed in a reproduction center between March 2018 and October 2020 which included 977 Japanese patients with normal ovarian reserve undergoing PPOS with CMA (n = 299), or GnRH antagonist (GnRH-ant) with cetrorelix (n = 608) in their first IVF cycle at the reproduction center. In subgroup analysis, pregnancy outcomes after frozen embryo transfers (FET) between PPOS (n = 284) and GnRH-ant (n = 579) were also compared. Participants/materials, setting, methods The inclusion criteria were patients aged &amp;lt; 40 years and AMH ≧ 1.1 ng/mL, who underwent autologous oocyte retrieval in their first IVF cycle with freeze-all strategy. The primary outcome was the incidence of premature LH surge, the secondary outcomes was oocyte maturation rate. To reduce the impact of treatment bias and potential confounding factors, we conducted logistic regression models with inverse-probability-of-treatment weighting (IPTW). Main results and the role of chance After IPTW, baseline clinical data were well-balanced between the two groups, including age, AMH, BMI, the duration, type, and cause of infertility, antral follicle count, the history of recurrent spontaneous abortion, and previous IVF attempts. The premature LH surge rate was significantly lower with PPOS (3.1%) compared to GnRH-ant (20.1%) (odds ratio, 0.21; 95% confidence interval, 0.11–0.36). No significant differences were found in total gonadotropin dose (2400IU for PPOS vs 2400IU for GnRH-ant, p = 0.136), the number of oocyte retrieval (n = 15 vs n = 15, p = 0.484), oocyte maturation rate (78.8% vs 77.8%, p = 0.275), fertilization rate (73.0% vs 72.0%, p = 0.412), viable embryo rate per oocyte retrieval (40% vs 40%, p = 0.890), and good quality blastocyst rate (72.0% vs 69.6%, p = 0.092). However, the good quality day-3 embryo rate was significantly lower with PPOS (37.2% vs 49.1%, p &amp;lt; 0.05). There were no differences in the incidence of moderate-to-severe OHSS (0.3% vs 0.7%, p = 0.481). In FET cycles, the pregnancy outcomes, such as implantation rate (43.1 % vs 51.9 %, p = 0.013) and clinical pregnancy rate (46.5% vs 54.7%, p = 0.027) were significantly lower with PPOS, however, no significant differences were found in ongoing pregnancy rate (75.6% vs 80.5%, p = 0.325), and live birth rate (72.4% vs 79.5 %, p = 0.142). Limitations, reasons for caution This was a retrospective cohort study conducted in a single center. The participants in this study were limited to Japanese ethnicity. The results need to be validated across different centers and other ethnicities. Wider implications of the findings This is the first report assessing the reproductive outcomes on PPOS using CMA, widely used in Japan. The PPOS with CMA significantly suppressed the premature LH surge rate compared to GnRH-ant protocol, without decrease in oocyte maturation rate. Trial registration number N/A

O-210 Cluster analysis reveals two hidden subgroups among patients with cryptozoospermia

Abstract Study question Can cryptozoospermic patients be sub classified based on clinical parameters? Summary answer Cryptozoospermic patients can be subdivided in two subgroups based on the histological phenotype of their testicular tissues, testicular volume and FSH levels. What is known already Cryptozoospermia is a severe form of oligozoospermia in which patients present with a sperm concentration of ≤ 0.1 million per milliliter. Due to such low sperm concentration, cryptozoospermic patients depend on the surgical procedure of testicular sperm extraction (TESE) to retrieve sperm for intracytoplasmic sperm injection (ICSI). The general etiology underlying cryptozoospermia remains hitherto unknown, likely due to the high heterogeneity within this patient cohort regarding histological and endocrine parameters. Study design, size, duration We retrospectively selected 132 cryptozoospermic patients (Crypto) who underwent TESE during their fertility treatment. Exclusion parameters were genetic diseases, a history of cryptorchidism or tumors and hormonal treatment. As controls, we selected 160 patients with obstructive azoospermia and normal spermatogenesis. All 292 patients were used for principal component analysis (PCA) followed by hierarchical clustering on principal components (HCPC). Participants/materials, setting, methods PCA and hierarchical clustering were performed considering age, testicular volume, hormonal values (FSH, LH, testosterone and free testosterone), ejaculate parameters (Ejaculate pH and volume, sperm concentration and total sperm count) and histological information. Histological analyses were performed on two PAS-stained sections from two independent biopsies per testis and patient. The percentage of seminiferous tubules containing elongated spermatids, round spermatids, spermatocytes or spermatogonia, as well as Sertoli cell only and hyalinized tubules was assessed. Main results and the role of chance The PCA and hierarchical clustering subdivided the patient cohort into 3 different clusters. Cluster 1 included all the controls (n = 160) and 2 Crypto patients. Remaining Crypto patients were equally subdivided between cluster 2 (n = 65) and cluster 3 (n = 65). The control patients in cluster 1 were characterized by the highest percentages of tubules with elongated spermatids (&amp;gt;80%), normal testicular volume and hormonal values. Characteristic of Crypto patients in cluster 2 was the arrest of germ cell differentiation at the level of spermatocytes in the majority of seminiferous tubules. In contrast, the majority of seminiferous tubules in Crypto patients in cluster 3 showed a Sertoli cell only phenotype or even tubular shadows. Interestingly, the more severe histological phenotype of the cluster 3 patients was accompanied by higher FSH and LH levels as well as lower testicular volume compared to cluster 2 patients. Despite this, the percentage of tubules with full spermatogenesis was similar in the two Crypto groups and no difference was found in the sperm retrieval rate after TESE in the two patient groups. Limitations, reasons for caution Uncovering the existence of subgroups within the cohort of Crypto-patients is the prerequisite for unveiling potentially distinct etiologies. Comprehensive genetic and scRNA-seq analyses of these Crypto-subgroups remain to be performed to validate the findings. Wider implications of the findings Overall, this study offers novel approaches towards the understanding of the etiology underlying the reduced sperm formation in Crypto patients and the division into two subgroups will facilitate the strategic search for underlying causes. Moreover, this approach could be applied to any infertility type in order to identify hidden subgroups. Trial registration number not applicable

Immunoregulatory Therapy Improves Reproductive Outcomes in Elevated Th1/Th2 Women with Embryo Transfer Failure.

Objective Immunological disturbance is one of the crucial factors of implantation failure. Limited data exists evaluating immunoregulatory therapy in patients with implantation failures. Methods This is a retrospective cohort study on patients who had failed embryo transfer cycle and had elevated Th1/Th2 cytokine ratios between 1/2019 and 3/2020. Patients were assigned into two groups based on whether they received immunoregulatory treatment during a frozen transfer cycle. The primary outcome was live birth rate. Secondary outcomes included clinical pregnancy, implantation rate, and neonatal outcomes. Results Of 71 patients enrolled, 41 patients received immunoregulatory therapy and 30 patients did not. Compared to untreated patients, rate of live birth was significantly elevated in the treated group (41.5% vs. 16.7%, P = 0.026). Rate of biochemical pregnancy, implantation, clinical pregnancy, and ongoing pregnancy between two groups were 56.1% vs. 40% (P = 0.18), 36.5% vs. 23.9% (P = 0.15), 51.2% vs. 30% (P = 0.074), and 41.5% vs. 16.7% (P = 0.03), respectively. Although there was no statistical significance, women receiving treatment also had a tendency of lower frequency of pregnancy loss (19.0% vs. 44.4%, P = 0.20). No adverse events were found between newborns of the two groups. Immunoregulatory therapy, age, infertility type, ovulation induction protocol, number of oocytes retrieved, artificial cycle embryo transfer, and cleavage transfer were associated with live birth in univariate analysis (all P < 0.05). Only immunoregulatory therapy was associated with live birth after adjustment of confounders (OR = 5.02, 95% CI: 1.02-24.8, P = 0.048). Conclusions Immunoregulatory therapy improves reproductive outcomes in elevated Th1/Th2 cytokine ratio women with embryo transfer failure.