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This study aims to investigate alterations in immune cell counts within preovulatory follicles of patients with poor ovarian response (POR) during assisted reproductive technology (ART), classified according to the POSEIDON criteria. Methods: This single-centre cross-sectional study included 543 women undergoing IVF/ICSI treatment, selected based on specific inclusion and exclusion criteria: 292 with normal ovarian response and 251 with poor response. Follicular fluid (FF) was collected on the day of oocyte retrieval and analysed by flow cytometry to determine the proportions of macrophages (Ms), M1 and M2 Ms, T cells (CD4 and CD8 T cells), dendritic cells (DCs), including type 1 conventional dendritic cells (cDC1) and type 2 conventional dendritic cells (cDC2), and neutrophils. Multivariable logistic regression assessed the relationship between immune cell counts and POR, Pearson correlation determined associations with the number of retrieved oocytes, and receiver operating characteristic (ROC) curves evaluated the predictive power of immune cell counts for POR. Results: Immune cells accounted for 52.57% (± 23.90%) of the total cell population in the follicular microenvironment, which was approximately equal to that of granulosa cells, with Ms being the most abundant, followed sequentially by T cells, DCs, and neutrophils. In patients with POR, overall Ms infiltration in the follicular microenvironment decreased, whereas M1 and M2 polarization increased. T cell infiltration increased, with a decrease in the CD4/CD8 ratio. Both cDC1 and cDC2 were significantly elevated. Moreover, multivariable logistic regression revealed that the total macrophage count, CD4 T cell count, and cDC2 count were independent predictors of POR. Notably, cDC2 showed the largest area under the ROC curve, suggesting its strong potential as a biomarker for predicting POR. Conclusion: The proportion of immune cells in preovulatory follicles were significantly altered in patients with POR. These findings suggest that immune cell dynamics in the follicular microenvironment may play a crucial role in determining ovarian response and prognosis, indicating that targeted immunomodulatory strategies could be considered in future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR). Methods: This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (=7) and high FR (>60%). Results: For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10 (TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]. Conclusions: TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR. [ABSTRACT FROM AUTHOR]

BACKGROUND: Controlled ovarian hyperstimulation has gradually become a routine method to increase the number of oocytes retrieved, but there has been controversy over whether the more oocytes retrieved the better. There is still no unified conclusion about the ideal range of egg retrieval number. OBJECTIVE: To explore the effect of number of oocytes retrieved on embryo fertilization outcome and clinical pregnancy outcome in fertilization in vitro treatment cycle. METHODS: 489 patients undergoing in vitro fertilization treatment (including conventional in vitro fertilization and intracytoplasmic sperm injection) were divided into the following five groups according to the number of oocytes retrieved: 1-4 group, 5-8 group, 9-12 group, 13-16 group, and ≥17 group. The fertilization rate, cleavage rate, transferable embryo rate, high-quality embryo rate, and clinical pregnancy outcome were compared in each group, and the effect of the number of oocytes retrieved on the outcome of in vitro fertilization was analyzed. RESULTS AND CONCLUSION: The number of oocytes retrieved was significantly correlated with the normal fertilization rate, transferable embryo rate, and high-quality embryo rate. Too many or too few retrieved oocytes could lead to a decrease in the normal fertilization rate and an increase in the abnormal fertilization rate, a decrease in the rates of transferable embryos and high-quality embryos, a decrease in the clinical pregnancy rates, embryo implantation rates, and live birth rates. In conclusion, too many or too few oocytes retrieved can lead to the decline of embryo quality and affect the clinical outcome of in vitro fertilization. The number between 5 and 16 oocytes may be appropriate, while the number between 9 and 12 oocytes may be optimal. During ovulation induction, clinicians should not only aim to increase the number of oocytes retrieved, but should pursue enough high-quality oocytes to reasonably formulate personalized ovulation induction programs for different patients. [ABSTRACT FROM AUTHOR]

Abstract Background No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS. Methods A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was > 10 IU/L, and/or a follicle with mean diameter > 12 mm was present, and/or serum E2 was > 600 pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group. Result(s) No significant difference was observed between the fixed and flexible groups regarding the number of oocytes retrieved (16.72 ± 7.25 vs. 17.47 ± 5.88, P = 0.421), the Gonadotropin treatment duration (9.53 ± 1.07 vs. 9.67 ± 1.03, P = 0.346) and total Gonadotropin dose (1427.75 ± 210.6 vs. 1455.94 ± 243.44, P = 0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57 ± 1.17 vs 6.04 ± 1.03, P = 0.001). There was no premature LH surge in either protocol. Conclusion(s) Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration. Trial registration NCT02635607 posted on December 16, 2015 in clinicaltrials.gov.

Study Question: Does luteal phase estrogen valerate pretreatment improve oocyte yield and clinical outcomes in patients with low ovarian response during ovarian stimulation with the antagonist protocol?Summary Answer: Pretreatment with oral estrogen valerate from Day 7 after ovulation to Day 2 of the next menstrual cycle did not increase oocyte yield in patients with a low ovarian response compared to no pretreatment.What Is Known Already: Previous studies showed that patients with a normal ovarian response can obtain better clinical outcomes after pretreatment with estrogen in the antagonist protocol. For patients with advanced age and low ovarian response, it remains unclear if estrogen valerate pretreatment with the antagonist protocol yields more oocytes and improves pregnancy outcomes.Study Design, Size, Duration: This non-blinded randomized controlled trial (RCT) was conducted between November 2017 and March 2021. Participants were 552 women with low response who requested IVF treatment. The primary endpoint was comparison of the total number of retrieved oocytes between the two groups. The secondary endpoints were the total number of retrieved metaphase II (MII) oocytes, duration and total dosage of recombinant FSH (rFSH), good-quality embryo rate and clinical pregnancy rate.Participants/materials, Setting, Methods: The study was conducted at a reproductive center. The RCT enrolled 552 infertile women with a low ovarian response (according to the Bologna criteria) who were undergoing IVF. In the study group, on Day 7 after ovulation patients were administered oral estrogen valerate (2 mg twice a day) until Day 2 of their next menstruation. Ovary stimulation was performed using rFSH, and a GnRH antagonist (0.25 mg/day) was started when a dominant follicle had a mean diameter ≥13 mm.Main Results and the Role Of Chance: No significant difference was observed in the number (mean [SD]) of oocytes retrieved from the estrogen valerate pretreatment and control group (3.2 [2.8] versus 3.4 [2.6], respectively). The treatment difference was -0.18 (95% CI -0.67, 0.32, P = 0.49). No significant differences were observed in the number of MII oocytes (2.9 [2.5] versus 3.1 [2.4], mean difference -0.23, 95% CI (-0.69, 0.23), P = 0.16) and good-quality embryos (1.0 [1.3] versus 1.20 [1.6], mean difference -0.23, 95% CI (-0.50, 0.04), P = 0.19) between the two groups. The duration of rFSH treatment was significantly longer in the estrogen valerate pretreatment group than in the control group (10.3 [2.2] versus 8.6 [2.1] days, mean difference 1.7, 95% CI (1.3, 2.2), P = 0.00), and the total rFSH dosage was significantly higher in the estrogen valerate pretreatment group than in the control group (3081 [680] versus 2548 [649] IU, mean difference 553.7, 95% CI (405.8, 661.6), P = 0.00). The clinical pregnancy rate in the pretreatment group (19.3% [23/119]) was not significantly different from that in the control group (28.7% [43/150]). The mean difference was -0.09, 95% CI (-0.20, 0.01), P = 0.08.Limitations, Reasons For Caution: The major limitation was the high dropout rate of patients. Some patients did not return to the hospital for treatment because of predicted low success rates and for economic reasons. In addition, it is possible that the fixed dose of 300 IU rFSH was not sufficient to see differences in oocyte yield between the groups.Wider Implications Of the Findings: Estrogen valerate pretreatment with an antagonist protocol did not increase oocyte yield in patients with low ovarian response. Similar to the number of retrieved oocytes, there was no significant difference in clinical pregnancy rate between estrogen pretreatment group and control group. More research is needed on whether patients with low ovarian response need pretreatment and which pretreatment is more appropriate.Study Funding/competing Interest(s): This study was supported in part by a research grant from the Investigator-Initiated Studies Program of MSD (China) Holding Co., Ltd. and Organon (Shanghai) Pharmaceutical Technology Co., Ltd. (Grant number: IIS 56284). The authors declare that they have no competing interests regarding authorship or publication of this study.Trial Registration Number: ClinicalTrials.gov NCT03300518.Trial Registration Date: 28 September 2017.Date Of First Patient’s Enrolment: 15 November 2017. [ABSTRACT FROM AUTHOR]

Aims: This study aims to determine the optimal number of oocytes retrieved so that patients with polycystic ovary syndrome (PCOS) receiving in vitro fertilization (IVF) can obtain the best cumulative live birth rate (CLBR) and live birth after fresh embryo transfer. Methods: This is a retrospective study of 1,419 patients with PCOS who underwent their first IVF cycle at the Second Hospital of Hebei Medical University from January 2014 to December 2021. Multivariable regression analysis was performed to adjust for factors known to independently affect cumulative live birth aspiration. The number of oocytes retrieved to obtain the best cumulative live birth rate was explored through curve fitting and threshold effect analysis. The decision tree method was used to explore the best number of oocytes retrieved to achieve live birth in the shortest time. Results: (1) The number of oocytes retrieved was found to be an independent protective factor for the cumulative live birth rate (OR = 1.09 (95% CI: 1.06, 1.12)). When the number of oocytes retrieved was less than 15, CLBR increased by 16% with each increase in the number of oocytes retrieved (OR = 1.16 (95% CI: 1.11, 1.22)); and when more than 15, CLBR tended to be stable. (2) Live birth after the first fresh embryo transfer was analyzed through a classification decision tree. For patients younger than 35 years old, those with less than 6 oocytes and those with 7–16 oocytes had a similar proportion of live births with fresh embryo transfer but higher than 16 oocytes (53.7% vs. 53.8% vs. 18.4%). Patients older than 35 years old had a similar proportion of live births with fresh embryo transfer (35.7% vs. 39.0%) to those younger than 35 years old, but the proportion of no live births after using up all embryos was higher than those younger than 35 years old (39.3% vs. 19.2%). Conclusions: In PCOS patients, high CLBR can be obtained when the number of oocytes retrieved was 15 or more. The number of oocytes retrieved from 7 to 16 could achieve more chance of live birth after fresh embryo transfer. [ABSTRACT FROM AUTHOR]

AimsThis study aims to determine the optimal number of oocytes retrieved so that patients with polycystic ovary syndrome (PCOS) receiving in vitro fertilization (IVF) can obtain the best cumulative live birth rate (CLBR) and live birth after fresh embryo transfer.MethodsThis is a retrospective study of 1,419 patients with PCOS who underwent their first IVF cycle at the Second Hospital of Hebei Medical University from January 2014 to December 2021. Multivariable regression analysis was performed to adjust for factors known to independently affect cumulative live birth aspiration. The number of oocytes retrieved to obtain the best cumulative live birth rate was explored through curve fitting and threshold effect analysis. The decision tree method was used to explore the best number of oocytes retrieved to achieve live birth in the shortest time.Results(1) The number of oocytes retrieved was found to be an independent protective factor for the cumulative live birth rate (OR = 1.09 (95% CI: 1.06, 1.12)). When the number of oocytes retrieved was less than 15, CLBR increased by 16% with each increase in the number of oocytes retrieved (OR = 1.16 (95% CI: 1.11, 1.22)); and when more than 15, CLBR tended to be stable. (2) Live birth after the first fresh embryo transfer was analyzed through a classification decision tree. For patients younger than 35 years old, those with less than 6 oocytes and those with 7–16 oocytes had a similar proportion of live births with fresh embryo transfer but higher than 16 oocytes (53.7% vs. 53.8% vs. 18.4%). Patients older than 35 years old had a similar proportion of live births with fresh embryo transfer (35.7% vs. 39.0%) to those younger than 35 years old, but the proportion of no live births after using up all embryos was higher than those younger than 35 years old (39.3% vs. 19.2%).ConclusionsIn PCOS patients, high CLBR can be obtained when the number of oocytes retrieved was 15 or more. The number of oocytes retrieved from 7 to 16 could achieve more chance of live birth after fresh embryo transfer.

Objective: To investigate cumulative live birth rate (cLBR) per oocyte retrieval in infertile patients aged 40 years and over undergoing their first in vitro fertilization/intracytoplasmic sperm injection cycles and to identify the possible predictors. Methods: A total of 1,613 patients at a university hospital in China from January 2013 to May 2017 were enrolled in this retrospective study. All data for fresh and subsequent frozen-thawed cycles were analyzed. Multivariate logistic regression analysis with stepwise selection of possible predictors for cLBR was performed, and Loess curve was constructed to determine the association between cLBR and the number of oocytes retrieved. Results: cLBR significantly increased with the number of oocytes retrieved and reached up to 75% when > 20 oocytes were retrieved ( P < 0.001). Variables of antral follicle count (AFC) and the number of oocytes retrieved were selected using multiple logistic regression analysis with stepwise selection to predict the significance of cLBR. cLBR demonstrated an obvious upward trend as the number of oocytes retrieval increased in the Loess curve. Conclusions: For patients aged 40 years and over, AFC and the number of oocytes retrieved were two key predictors for cLBR and maximization of ovarian reserve exploitation was pivotal to increase the chance of live birth.

Background: No previous study directly compares the fixed day-5 initiation versus the flexible initiation of GnRH antagonist administration in IVF/ICSI for those patients who are predicted as high ovarian responders without PCOS. To evaluate whether the number of oocytes retrieved is different by using the two GnRH antagonist protocols in Chinese women with predicted high ovarian response except PCOS.Methods: A randomized controlled trial of 201 infertile women with predicted high ovarian response except PCOS undergoing in vitro fertilization. Ovary stimulation was performed using recombinant FSH and GnRH antagonists. GnRH antagonist ganirelix (0.25 mg/d) was started either on day 5 of stimulation (fixed group) or when LH was > 10 IU/L, and/or a follicle with mean diameter > 12 mm was present, and/or serum E2 was > 600 pg/ml. Patient monitoring was initiated on day 3 of stimulation in flexible group.Result(s): No significant difference was observed between the fixed and flexible groups regarding the number of oocytes retrieved (16.72 ± 7.25 vs. 17.47 ± 5.88, P = 0.421), the Gonadotropin treatment duration (9.53 ± 1.07 vs. 9.67 ± 1.03, P = 0.346) and total Gonadotropin dose (1427.75 ± 210.6 vs. 1455.94 ± 243.44, P = 0.381). GnRH antagonist treatment duration in fixed protocol was statistically longer than the flexible protocol (6.57 ± 1.17 vs 6.04 ± 1.03, P = 0.001). There was no premature LH surge in either protocol.Conclusion(s): Fixed GnRH antagonist administration on day 5 of stimulation appear to achieve a comparable oocyte retrieved compared with flexible antagonist administration.Trial Registration: NCT02635607 posted on December 16, 2015 in clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Appropriate ovarian responses to the controlled ovarian stimulation strategy is the premise for a good outcome of the in vitro fertilization cycle. With the booming of artificial intelligence, machine learning is becoming a popular and promising approach for tailoring a controlled ovarian stimulation strategy. Nowadays, most machine learning-based tailoring strategies aim to generally classify the controlled ovarian stimulation outcome, lacking the capacity to precisely predict the outcome and evaluate the impact features. Based on a clinical cohort composed of 1365 women and two machine learning methods of artificial neural network and supporting vector regression, a regression prediction model of the number of oocytes retrieved is trained, validated, and selected. Given the proposed model, an index called the normalized mean impact value is defined and calculated to reflect the importance of each impact feature. The proposed models can estimate the number of oocytes retrieved with high precision, with the regression coefficient being 0.882% and 89.84% of the instances having the prediction number ≤ 5. Among the impact features, the antral follicle count has the highest importance, followed by the E2 level on the human chorionic gonadotropin day, the age, and the Anti-Müllerian hormone, with their normalized mean impact value > 0.3. Based on the proposed model, the prognostic results for ovarian response can be predicted, which enables scientific clinical decision support for the customized controlled ovarian stimulation strategies for women, and eventually helps yield better in vitro fertilization outcomes.

Background: Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine.Objective and Rationale: The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included.Search Methods: Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217).Outcomes: Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls).Wider Implications: For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses. [ABSTRACT FROM AUTHOR]