UNASSIGNED: To determine whether endometrial thickness (EMT) differs between i) clomiphene citrate (CC) and gonadotropin (Gn) utilizing patients as their own controls, and ii) patients who conceived with CC and those who did not. Furthermore, to investigate the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles.
UNASSIGNED: Retrospective study. Three sets of analyses were conducted separately for the purpose of this study. In analysis 1, we included all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307), to compare EMT differences between CC/IUI and Gn/IUI, utilizing women as their own controls. In analysis 2, we included all CC/IUI cycles (CC2, n=686) from women who eventually conceived with CC during the same study period, to evaluate EMT differences between patients who conceived with CC (CC2) and those who did not (CC1). In analysis 3, pregnancy outcomes among different EMT quartiles were evaluated in CC/IUI and Gn/IUI cycles, separately, to investigate the potential association between EMT and pregnancy outcomes.
UNASSIGNED: In analysis 1, when CC1 was compared to Gn1 cycles, EMT was noted to be significantly thinner [Median (IQR): 6.8 (5.5-8.0) vs. 8.3 (7.0-10.0) mm, p<0.001]. Within-patient, CC1 compared to Gn1 EMT was on average 1.7mm thinner. Generalized linear mixed models, adjusted for confounders, revealed similar results (coefficient: 1.69, 95% CI: 1.52-1.85, CC1 as ref.). In analysis 2, CC1 was compared to CC2 EMT, the former being thinner both before [Median (IQR): 6.8 (5.5-8.0) vs. 7.2 (6.0-8.9) mm, p<0.001] and after adjustment (coefficient: 0.59, 95%CI: 0.34-0.85, CC1 as ref.). In analysis 3, clinical pregnancy rates (CPRs) and ongoing pregnancy rates (OPRs) improved as EMT quartiles increased (Q1 to Q4) among CC cycles (p<0.001, p<0.001, respectively), while no such trend was observed among Gn cycles (p=0.94, p=0.68, respectively). Generalized estimating equations models, adjusted for confounders, suggested that EMT was positively associated with CPR and OPR in CC cycles, but not in Gn cycles.
UNASSIGNED: Within-patient, CC generally resulted in thinner EMT compared to Gn. Thinner endometrium was associated with decreased OPR in CC cycles, while no such association was detected in Gn cycles.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient.
METHODS: We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate.
CONCLUSIONS: The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET.
BACKGROUND: Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.

The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option.Clinical trial registration: https://www.chictr.org.cn/ , identifier [ChiCTR2300076537].

OBJECTIVE: Polycystic ovary syndrome (PCOS) is an endocrine gynecological disease affecting many women of reproductive age. Clomiphene is the first-line treatment for PCOS patients, but most individuals may be resistant to it. This study aims to assess the efficacy of dexamethasone and clomiphene in the treatment of PCOS patients, and to provide a theoretical basis for clinicians to study and treat PCOS.
METHODS: Chinese and English databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang Medical Network, and VIP Information Chinese Journal Service Platform (VIP) were searched from the inception to January 2023. Review Manager and Stata software were used for meta- analysis. The risk of bias of eligible studies were assessed using Cochrane\'s risk of bias tool. Publication bias was assessed by funnel plots, Begg\'s and Egger\'s tests.
RESULTS: A total of 12 literatures were finally included, with a total of 1270 PCOS patients. Compared with the control group, dexamethasone combined with clomiphene could significantly improve pregnancy (RR = 1.71, P < 0.00001), ovulation (RR = 1.30, P < 0.00001), luteinizing hormone level (SMD = -0.94, P < 0.00001), estradiol level (SMD = 0.99, P = 0.05), progesterone level (SMD = 5.08, P = 0.002) and testosterone level (SMD = -1.59, P < 0.00001). However, there were no significant effects on ovulation-stimulating hormone level (SMD = 0.15, P = 0.37), adverse reactions (RR = 1.30, P = 0.30), dizziness (RR = 1.50, P = 0.45), and vomiting (RR = 1.67, P = 0.48).
CONCLUSIONS: The treatment of dexamethasone combined with clomiphene is helpful to improve the ovulation and pregnancy rate in patients with PCOS, and improve the hormone levels of patients.

OBJECTIVE: To compare the pregnancy outcomes of luteal phase and follicular phase progestin-primed ovarian stimulation protocol with clomiphene citrate supplementation (LPPOS+CC and FPPOS+CC) in young women with diminished ovarian reserve (DOR).
METHODS: A total of 483 women aged ≤35 years with DOR, who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) with controlled ovarian stimulation using LPPOS+CC (n=257) or FPPOS+CC (n=226) protocols during June 2018 and December 2021 at the First Affiliated Hospital of Wenzhou Medical University, were included in this retrospective study. The baseline characteristics, superovulation results, laboratory related indicators between the two groups, and the pregnancy outcomes of women who achieved at least one high-quality cleavage-stage embryo or good-morphology blastocyst were compared between the two groups.
RESULTS: No statistically significant differences were identified between the groups with respect to age, duration of infertility, proportion of secondary infertility, previous failed cycles, body mass index, anti-Müllerian hormone, antral follicle count, basal luteinizing hormone level, basal progesterone level, number of oocytes retrieved, oocyte maturation rate, high-quality cleavage-stage embryo cycle rate, the percentage of women with profound pituitary suppression, live birth rate and preterm birth rate (all P>0.05). The LH levels on the day of trigger [4.0 (2.7, 5.3) vs. 5.1 (3.2, 7.2) IU/L], the percentage of women with LH levels of >10 IU/L on the trigger day (3.13% vs. 10.67%), and the two pronucleus (2PN) rate of ICSI oocytes (72.16% vs. 79.56%) were significantly lower in the LPPOS+CC group than those in the FPPOS+CC group (P<0.05 or P<0.01). The duration of stimulation [11 (9, 12) vs. 9 (8, 11) d], the consumption of total gonadotropin [2213 (1650, 2700) vs. 2000 (1575, 2325) IU], the progesterone levels on the day of trigger [1.3 (0.8, 2.9) vs. 0.9 (0.6, 1.2) ng/mL], the clinical pregnancy rate [61.88% vs. 46.84%], and implantation rate [42.20% vs. 31.07%] in the LPPOS+CC group were significantly higher than those in the FPPOS+CC group (all P<0.01).
CONCLUSIONS: Compared to FPPOS+CC, the LPPOS+CC protocol appears to have better pregnancy outcomes for young women with DOR undergoing IVF/ICSI-ET.
目的: 比较卵泡期和黄体期启动高孕激素状态超促排卵（PPOS）方案在35岁及以下卵巢储备功能减退（DOR）患者中的应用效果。方法: 回顾性分析2018年6月至2021年12月在温州医科大学附属第一医院生殖医学中心采用PPOS方案行体外受精/卵胞质内单精子注射-胚胎移植的483例35岁及以下DOR患者的资料，其中采用卵泡期PPOS方案226例（FPPOS+CC组），黄体期PPOS方案257例（LPPOS+CC组）。比较两组的基线特征、超促排卵结果和实验室相关指标，并比较获得第三天（以下简称D3）优质胚胎的患者超促排卵后第一次冻融胚胎移植的妊娠结局。结果: 两组间年龄、不孕年限、继发不孕占比、既往治疗周期数、体重指数、抗米勒管激素、窦状卵泡数、基础黄体生成素、基础孕酮水平、平均获卵数、MⅡ卵率、D3优质胚胎率、深度垂体抑制发生率、活产率和早产率等差异均无统计学意义（均P>0.05）。与FPPOS+CC组比较，LPPOS+CC组诱发排卵日黄体生成素（LH）水平［分别为4.0（2.7，5.3）和5.1（3.2，7.2）IU/L］、早发LH峰发生率（分别为3.13%和10.67%）、卵胞质内单精子注射双原核受精率（分别为72.16%和79.56%）均更低（P<0.05或P<0.01），而促性腺激素（Gn）天数［分别为11（9，12）和9（8，11）d］、Gn总量［分别为2213（1650，2700）和2000（1575，2325）IU］、诱发排卵日孕酮水平［分别为1.3（0.8，2.9）和0.9（0.6，1.2）ng/mL］、冻融胚胎移植的临床妊娠率（分别为61.88%和46.84%）和着床率（分别为42.20%和31.07%）均更高（均P<0.01）。结论: 35岁及以下DOR患者采用LPPOS+CC方案后冻融胚胎移植临床妊娠结局更佳。.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of childbearing age and is the primary cause of anovulatory infertility, accounting for 70% to 80% of cases. Ovulation induction is the main treatment approach for infertile patients with PCOS. Commonly utilized medications for this purpose are clomiphene citrate (CC) and letrozole (LE). Clomiphene citrate administration results in an ovulation rate ranging from 60% to 85%, while the pregnancy rate is limited to 35% to 40%, and a further reduction is observed in live birth rates. Letrozole demonstrates a slightly higher pregnancy rate and live birth rate compared to clomiphene citrate, although challenges persist in terms of longer stimulation cycles, multiple pregnancies, and the risk of ovarian hyperstimulation syndrome (OHSS). Clinical reports indicate that acupuncture therapy shows promising efficacy in treating patients with PCOS-related infertility, despite a partially unclear understanding of its underlying mechanisms.
METHODS: In this study, one patient did not achieve pregnancy despite more than a year of ovulation induction using clomiphene citrate and letrozole. However, after 3 months of receiving cheek acupuncture therapy, she successfully conceived and gave birth to a liveborn baby. Another patient achieved natural conception and live birth after 2 months of exclusive cheek acupuncture therapy.
METHODS: PCOS.
METHODS: Cheek acupuncture therapy.
RESULTS: Both of them successfully conceived and gave birth to a liveborn baby.
CONCLUSIONS: These findings suggest that cheek acupuncture therapy can effectively stimulate follicle development and ovulation, potentially improving endometrial receptivity. According to holographic theory, there is a biologically holographic model within the cheek region that shares a homology with the human body structure. This model provides an explanation for the regulatory effects of cheek acupuncture point stimulation on the Hypothalamic-Pituitary-Ovarian axis (HPO), which subsequently influences follicle development and ovulation in patients. Consequently, when cheek acupuncture therapy is applied alone or in combination with ovulation induction medication, patients have the ability to achieve successful pregnancy and experience a smooth delivery.

In infertile women with polycystic ovary syndrome (PCOS), is the sequential use of letrozole 2.5 mg/follicle stimulating hormone(FSH) more effective than letrozole 5 mg/FSH in stimulating ovulation and promoting pregnancy?
The study was designed as a prospective, single-center, randomized, controlled pragmatic clinical trial. 220 infertile women between the ages of 20 and 40, who matched the Rotterdam criteria for PCOS and had no other identified reasons for infertility were enrolled from April 2023 to July 2023.The participants were randomly assigned to two groups in a 1:1 ratio. One group received 2.5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110), while the other group received 5 mg of letrozole on cycle days 3-7 with a sequential injection of 75 IU FSH on cycle days 8-10 (n = 110). The duration of FSH treatment varied depending on the follicular development stage. Each participant underwent one to three treatment cycles until achieving pregnancy.The primary outcome was the cumulative pregnancy rate of all the participants. Secondary outcomes included characteristics and clinical pregnancy rates of all the intervention cycles.
For all 220 participants, the sequential letrozole 2.5 mg/FSH treatment group had a significantly higher cumulative pregnancy rate compared to the letrozole 5 mg/FSH treatment group (72.7% versus 59.1%, RR (95%CI) = 1.23 (1.02, 1.49), P-value = 0.033). For all 468 intervention cycles, letrozole 2.5 mg/FSH group had a significantly higher clinical pregnancy rate than the letrozole 5 mg/FSH group (36.2% versus 26.3%, P-value = 0.021), no statistically significant differences were observed in ovulation rates or adverse effects.
The data indicate that the sequential letrozole 2.5mg/FSH protocol may be more effective than the sequential letrozole 5mg/FSH protocol for promoting pregnancy in infertile women with PCOS.
www.chictr.org.cn, identifier ChiCTR2300069638.

OBJECTIVE: To compare the live birth rate of the first frozen embryo transfer (FET) after ovarian stimulation by the progestin-primed ovarian stimulation (PPOS) protocol vs. the antagonist protocol in women with an anticipated high ovarian response who were undergoing in vitro fertilization.
METHODS: Randomized controlled trial.
METHODS: A tertiary assisted reproduction center.
METHODS: Women with infertility aged <43 years undergoing the first in vitro fertilization cycle and having antral follicle count of >15.
METHODS: Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the PPOS protocol. In the antagonist protocol, an antagonist 0.25 mg daily was given from the sixth day of ovarian stimulation until the day of ovulation trigger. Blinding was not possible for women or physicians but the biostatistician was blinded to the group assignment.
METHODS: Live birth rate of the first FET cycle.
RESULTS: A total of 784 women were recruited from June 2020 and October 2021 and assigned randomly in a 1:1 ratio into two groups: PPOS group (n = 392) and antagonist group (n = 392). Embryo transfer was either cancelled or postponed in 62 women (62/392, 15.8%) in the PPOS group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no FET within 6 months after randomization. The two groups were similar in demographic characteristics and the numbers of oocytes obtained or fertilized, cleaving embryos, good-quality embryos at day 3, blastocysts developed, and embryos or blastocysts frozen. There was no statistically significant difference in the live birth rate of the first FET cycle between the PPOS and antagonist groups on the basis of both the intention-to-treat analysis (37.5.0% [147/392] vs. 32.7% [128/392]; relative risk, 1.148 [95% confidence interval, 0.949-1.390]) and per-protocol analysis (44.5% [147/330] vs. 39.1% [128/327]; relative risk, 1.138 [95% confidence interval, 0.950-1.364]). Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy, and cumulative live birth rates.
CONCLUSIONS: The live birth rates of the first FET following the PPOS and antagonist protocols were comparable in women with an anticipated high ovarian response.
BACKGROUND: NCT04414761 (ClinicalTrials.gov).

To examine the effects of clomiphene citrate (CC) on follicular fluid metabolites and related metabolic pathways in rats with polycystic ovary syndrome (PCOS) using non-targeted metabolomics and determine how CC treats ovulation disorder in PCOS. The Sprague Dawley rats were randomly divided into control, model, and CC groups. A PCOS model was established with letrozole. Body weight, ovarian weight, estrus cycles, serum hormone levels, and ovary histopathology of the rats were collected for further evaluation. Moreover, through ultra-performance liquid chromatography-mass spectrometry, the study of follicular fluid metabolites revealed the mechanism of action of CC. CC reduced ovarian weight and regulated estrous cycles and serum hormone levels in PCOS rats but did not affect their body weight. Moreover, the metabolomic results showed that CC adjusted 153 metabolites, among which 16 cross metabolites like testosterone, androstenedione, 17α-hydroxyprogesterone, and cholic acid were considered as potential biomarkers for CC to improve ovulation disorders in PCOS rats. Kyoto Encyclopedia of Genes and Genomes pathway enrichment also showed that the CC group mainly engaged in tryptophan metabolism and steroid hormone biosynthesis. CC can improve ovulation disorders in rats, and its mechanism is related to the regulation of the secretion of serum hormone and follicular fluid metabolites and the amelioration of multi-metabolic pathways.

The purpose of this research was to evaluate the efficacy of 3 ovulation induction therapies for treating infertility in patients with polycystic ovary syndrome (PCOS). In this retrospective study, we compared the success rates of 90 patients who underwent intrauterine insemination, who were randomly assigned to 1 of 3 treatment groups: letrozole (LE) + urinary gonadotropin (human menopausal gonadotropin [HMG]), clomiphene (CC) + HMG, or HMG alone. Using ultrasound scanning, we examined the number of mature follicles, ovulation rate, clinical pregnancy rate, endometrial thickness, and blood flow. When compared to the other 2 groups, the LE + HMG group had significantly higher levels of mature follicles, ovulation rate, clinical pregnancy rate, estradiol, and luteinizing hormone on the day of the human chorionic gonadotropin injection and endometrial receptivity (P < .05). There was no statistically significant difference between the 3 groups in terms of abortion rate, ectopic pregnancy rate, or adverse reactions. In this research, we found that infertility in patients with PCOS could be effectively treated by combining LE with HMG. This protocol increased ovulation, boosted fertility, and enhanced endometrial receptivity with no increase in adverse reactions. Therefore, it may be a useful clinical approach for inducing ovulation and treating infertility in patients with PCOS.