Comparison of clinical outcomes and perinatal outcomes between natural cycle and hormone replacement therapy of frozen-thawed embryo transfer in patients with regular menstruation: a propensity score-matched analysis.

Purpose: To investigate potential differences in pregnancy outcomes among patients with regular menstruation who underwent frozen-thawed embryo transfer using natural cycle (NC) or hormone replacement therapy (HRT). Methods: This study retrospectively analyzed 2672 patients with regular menstruation who underwent FET from November 2015 to June 2021 at the single reproductive medical center. A one-to-one match was performed applying a 0.02 caliper with propensity score matching. Independent factors influencing the live birth and clinical pregnancy rates were screened and developed in the nomogram by logistic regression analysis. The efficacy of live birth rate and clinical pregnancy rate prediction models was assessed with the area under the ROC curve, and the live birth rate prediction model was internally validated within the bootstrap method. Results: The NC protocol outperformed the HRT protocol in terms of clinical pregnancy and live birth rates. The stratified analysis revealed consistently higher live birth and clinical pregnancy rates with the NC protocol across different variable strata compared to the HRT protocol. However, compared to the HRT treatment, perinatal outcomes indicated that the NC protocol was related to a higher probability of gestational diabetes. Multifactorial logistic regression analysis demonstrated independent risk factors for live birth rate and clinical pregnancy rate. To predict the two rates, nomogram prediction models were constructed based on these influencing factors. The receiver operating characteristic curve demonstrated moderate predictive ability with an area under curve (AUC) of 0.646 and 0.656 respectively. The internal validation of the model for live birth rate yielded an average AUC of 0.646 implying the stability of the nomogram model. Conclusion: This study highlighted that NC yielded higher live birth and clinical pregnancy rates in comparison to HRT in women with regular menstruation who achieved successful pregnancies through frozen-thawed embryo transfer. However, it might incur a higher risk of developing gestational diabetes.

Ibuprofen delays ovulation by several hours: prospective controlled study in natural cycles with HCG-triggered ovulation.

RESEARCH QUESTION: Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DESIGN: Two-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3 × 400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. RESULTS: A total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). CONCLUSIONS: Women trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.

The natural menstrual cycle revisited - can natural cycle be trusted.

BACKGROUND: The serum progesterone (P4) level during the luteal phase (LP) plays a crucial role in the initiation and maintenance of pregnancy. However, it is unclear whether the natural cycle consistently provides the best endocrine profile and whether mid-luteal serum P4 levels are always sufficient to support implantation and early pregnancy. The question has become more relevant in relation to fertility treatment, as more frozen embryo transfer cycles are performed in the natural cycle. Moreover, can serum hormone levels and covariates measured during the follicular phase (FP), such as Follicle Stimulation Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Anti-Mullerian Hormone (AMH) and Antral Follicle Count (AFC), be used to predict P4 levels during the luteal phase (LP)? RESULTS: This observational prospective cohort study analysed 26 healthy women with a cycle length between 21-35 days and a body mass index (BMI) < 30 kg/m2. Blood sampling started on the fifth day of the menstrual cycle and continued every fifth day until the next cycle. The procedure was repeated for a total of three cycles. The study found that only ten women had a P4 level greater than 30 nmol/L on cycle day 20 or 25 in all three cycles. In total, only 45 cycles out of 77 cycles had serum P4 levels ≥ 30 nmol/L. The E2 level ≥ 345 pmol/L on cycle day 10 proved to be predictive of a P4 level of ≥ 30 nmol/L on either day 20 or day 25 with a sensitivity of 57% and a specificity of 89%. No other covariates, including the FSH level cycle day 5, LH levels during the follicular phase, age, weight, AFC and AMH cycle day 5 correlated with LP P4 levels. CONCLUSIONS: A significant correlation between FP E2 levels cycle day 5 (> 131pmol/L) and cycle day 10 (> 345pmol/L) and a LP P4 level ≥ 30 nmol/l was found; thus, the FP E2 level is a predictor of corpus luteum competence. Our findings highlight the existence of suboptimal P4 levels during the LP and a significant inter-individual and intra-cycle variation in P4 levels during the LP in regular menstruating women.

Ongoing pregnancy rates in single euploid frozen embryo transfers remain unaffected by female age: a retrospective study.

RESEARCH QUESTION: Is female age a significant factor in the likelihood of an ongoing pregnancy in single euploid frozen embryo transfers (FET)? DESIGN: Retrospective study of 1923 single euploid FET cycles in 1464 women, either in a natural cycle or a hormone replacement therapy cycle. The primary outcome was the ongoing pregnancy rate (OPR). RESULTS: There were 990 (51.48%) ongoing pregnancies among 1923 included transfers. The OPR were 51.4%, 49.1%, 53.3% and 52.3% for women aged ≤35, >35-≤37, >37-≤40 and >40 years at oocyte retrieval (OCR), without a significant trend for decreasing OPR (P = 0.679). No significant differences in female age at embryo transfer (P = 0.609) and female age at OCR (P = 0.816) were found between the groups (ongoing pregnancy versus no pregnancy or miscarriage). Women who received good-quality embryos (P < 0.001), had a lower body mass index (BMI) (P < 0.001), had achieved at least one pregnancy previously (P < 0.001), and underwent natural cycle endometrial preparation (P < 0.001) were more likely to achieve an ongoing pregnancy. Multivariable regression analysis (adjusted for BMI, embryo quality and endometrial preparation) did not show a significant effect of female age at OCR on achieving an ongoing pregnancy. Compared with women aged ≤35 years, none of the age groups had significantly higher or lower OPR. A multinomial regression analysis showed that BMI, embryo quality and endometrial preparation were associated with miscarriage/no pregnancy versus ongoing pregnancy (P = 0.001, 0.001 and 0.001, respectively). Female age had no significant association with either outcome. CONCLUSIONS: Female age in itself does not have a substantial impact on the OPR in single euploid FET cycles, but the OPR is impacted significantly by embryo quality, BMI, previous parity, and a natural cycle endometrial preparation protocol.

Progesterone concentrations on blastocyst transfer day in modified natural cycle frozen embryo transfer cycles.

RESEARCH QUESTION: Are serum progesterone concentrations on the day of modified natural cycle (mNC) frozen blastocyst transfer (FET) without luteal phase support (LPS) associated with clinical pregnancy rate (CPR)? DESIGN: Data were collected between January 2019 and October 2022 as a sub-study of an ongoing randomized controlled trial assessing pregnancy outcomes in mNC-FET. The sub-study included all women (n = 209) randomized to mNC-FET without LPS at the time of data extraction. Participants were aged 18-41 years, had regular menstrual cycles and underwent mNC-FET treatment with single-blastocyst transfer. Associations between the serum progesterone concentration on the day of blastocyst transfer and CPR, pregnancy rate and pregnancy loss rate (PLR) were examined between groups with low and higher progesterone concentrations using the 25th and 10th percentiles as cut-offs. Multivariate logistic regression analyses were performed to adjust for potential confounding factors. RESULTS: Progesterone concentrations on the day of blastocyst transfer in mNC-FET without LPS ranged from 4.9 to 91.8 nmol/l, with the 25th and 10th percentiles at 29.0 nmol/l and 22.5 nmol/l, respectively. Serum progesterone concentrations did not differ between women with or without a clinical pregnancy (mean [SD] 38.5 [14.0] versus 36.8 [12.4] nmol/l; P = 0.350). Furthermore, the CPR, pregancy rate and PLR were similar in women with low or high progesterone concentrations when using the 25th or the 10th progesterone percentile as cut-off. Multivariate regression analyses showed no association between progesterone concentrations and CPR. CONCLUSIONS: No association was found between progesterone concentration on the day of blastocyst transfer and pregnancy outcome in women undergoing mNC-FET without progesterone LPS.

Circadian serum progesterone variations on the day of frozen embryo transfer in a modified natural cycle protocol.

STUDY QUESTION: Is there a circadian variation of serum progesterone (P) on the day of frozen embryo transfer (FET) in a modified natural cycle (mNC)? SUMMARY ANSWER: There is a statistically significant diurnal variation of serum P on the day of a FET in an mNC protocol. WHAT IS KNOWN ALREADY: In recent years, the proportion of FET cycles has increased dramatically. To further optimize pregnancy outcomes after FET, recent studies have focused on serum luteal P levels in both natural and artificially prepared FET cycles. Despite the different cut-off values proposed to define low serum P in the NC, it is generally accepted that lower serum P values (<10 ng/ml) around the day of FET are associated with negative reproductive outcomes. However, a single serum P measurement is not reliable given that P levels are prone to diurnal fluctuations and are impacted by patients' characteristics. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was conducted in a single university-affiliated fertility center, including 22 patients performing a single blastocyst mNC-FET from August 2022 to August 2023. Serum P levels were measured on the day of transfer at 08:00h, 12:00h, 16:00h, and 20:00h. Differences between P levels were compared using the Wilcoxon signed-rank test. The sample size was calculated to detect a difference of 15% between the first and last P measurements with a 5% false-positive rate and a 95% CI. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with a normal BMI, between 18 and 40 years old, without uterine diseases were eligible. Patients utilizing donated oocytes were excluded. The mNC-FET protocol involved monitoring the normal ovarian cycle and triggering ovulation with an injection of 250 µg of choriogonadotropin alfa when a pre-ovulatory follicle (16-20 mm diameter) was visualized. The blastocyst was transferred seven days later. The patients were not supplemented with exogenous P at any time before the day of the FET. MAIN RESULTS AND THE ROLE OF CHANCE: The mean age and BMI of the study population were 33.6 ± 3.8 years and 22.7 ± 1.8 kg/m2, respectively. Mean P values at 08:00h, 12:00h, 16:00h, and 20:00h were 14.6 ± 4.5, 14.7 ± 4.1, 12.9 ± 3.5, and 14.6 ± 4.3 ng/ml, respectively. The mean P levels at 16:00h were significantly lower compared to all other time points (P < 0.05: P = 0.007 between P at 8:00h and 16:00h; P = 0.003 between P at 12:00h and 16:00h; P = 0.007 between P at 16:00h and 20:00h). No statistically significant difference was observed between P values at the other time points (P > 0.05: P = 0.88 between P at 8:00h and 12:00h; P = 0.96 between P at 8:00h and 20:00h; P = 0.83 between P at 12:00h and 20:00h). LIMITATIONS, REASONS FOR CAUTION: The study's limitations include the small sample size that may cause a bias when the results are extrapolated to a larger subfertile population undergoing mNC-FET. Ideally, larger prospective trials including a more heterogeneous patient population would be necessary to validate our findings. WIDER IMPLICATIONS OF THE FINDINGS: The current study demonstrates the existence of a diurnal fluctuation of serum P on the day of mNC-FET highlighting the importance of a standardized time point for its measurement. This is especially important for considering clinical actions, such as additional exogenous P supplementation, when encountering P values lower than 10 ng/ml on the day of FET. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained for the study. The authors have no conflicts of interest to declare regarding the content of the study. TRIAL REGISTRATION NUMBER: NCT05511272.

Association between endometrial thickness and birthweight of singletons from vitrified-warmed cycles: a retrospective cohort study.

RESEARCH QUESTION: What is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles? DESIGN: This retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used. RESULTS: In the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17-2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03-3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles. CONCLUSIONS: A thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles.

Modified natural cycle allows a window of 7 days for frozen embryo transfer planning.

RESEARCH QUESTION: Should ovulation be triggered in a modified natural cycle (mNC) with recombinant human chorionic gonadotrophin (rHCG) as soon as a mean follicle diameter of 17 mm is visible, or is more flexible planning possible? DESIGN: This multicentre, retrospective, observational study of 3087 single frozen blastocyst transfers in mNC was carried out between January 2020 and September 2022. The inclusion criteria included endometrial thickness ≥7 mm and serum progesterone <1.5 ng/ml. The main outcome was ongoing pregnancy rate. Secondary end-points were pregnancy rate, implantation rate, clinical pregnancy rate and miscarriage rate. The mean follicle size at triggering was stratified into three groups (13.0-15.9, 16.0-18.9 and 19.0-22 mm). RESULTS: The baseline characteristics between the groups did not vary significantly for age, body mass index and the donor's age for egg donation. No differences were found in pregnancy rate (64.5%, 60.2% and 57.4%; P = 0.19), clinical pregnancy rate (60.5%, 52.8% and 50.6%; P = 0.10), implantation rate (62.10%, 52.9% and 51.0%; P = 0.05) or miscarriage rate (15.0%, 22.2%; and 25.0%; P = 0.11). Although ongoing pregnancy rate (54.9%, 46.8% and 43.1%; P = 0.02) varied significantly in the univariable analysis, it was no longer significant after adjustment for the use of preimplantation genetic testing for aneuploidies and egg donation. CONCLUSIONS: The findings showed rHCG could be flexibly administered with a mean follicle size between 13 and 22 mm as long as adequate endometrial characteristics are met, and serum progesterone is <1.5 ng/ml. Considering the follicular growth rate of 1-1.5 mm/day, this approach could allow a flexibility for FET scheduling of 6-7 days, simplifying mNC FET planning in clinical practice.

Clinical Outcomes in Hormone Replacement Therapy (HRT)-Frozen Embryo Transfer (FET) Protocol Increased by Administering Gonadotropin-Releasing Hormone Agonist (GnRH) in the Initial Stage of the Luteal Phase: A Retrospective Analysis.

OBJECTIVE: The objective of this study was to determine if gonadotropin-releasing hormone agonist (GnRH) administration supporting the luteal phase in frozen embryo transfer (FET) improves clinical outcomes Methods and materials This is a retrospective cohort study and we analyzed 3515 cycles of FET at the Department of Reproductive Medicine in our hospital from February 2018 through December 2021. Patients were divided into the GnRH (triptorelin+progesterone and human chorionic gonadotropin (hCG)) group and the non-GnRHa (existing treatment without triptorelin) group. There were 1033 and 2485 cases in the above groups, respectively. Live birth rates (LBR) and clinical pregnancy rates (CPR) were contrasted in the two groups. RESULTS: We found greater CPR (58.00% versus 48.40%, P-value = 0.003) and LBR (52.70% versus 45.60%, P-value = 0.001) for HRT-FET cycles, and found no clinical significance for natural cycle FET (NC-FET) (58.20% versus 52.90%, P-value = 0.364 and 54.40% versus 47.00%, P-value=0.211), GnRH+HRT-FET (53.00% versus 53.00%, P-value=0.176 and 46.20% versus 47.30%, P-value=0.794), and stimulation-FET (59.30% versus 52.90%, P-value=.00.566 and 59.30% versus 47.10%, P-value=.00.247) in terms of CPR and LBR in the two groups. There was a 47% increase in CPR in the GnRH group, and there was a 33% increase in LBR in the same group. CONCLUSION: During HRT-FET cycles, administering triptorelin three to four times in the existing luteal support can improve CPR and LBR, and administering triptorelin during the initial stage of the luteal phase can prove a new option for luteal support.

Natural proliferative phase frozen embryo transfer-a new approach which may facilitate scheduling without hindering pregnancy outcomes.

STUDY QUESTION: How does a natural proliferative phase (NPP) strategy for frozen embryo transfer (FET) compare with the conventional artificial (AC) and natural (NC) endometrial preparation protocols in terms of live birth rates (LBR)? SUMMARY ANSWER: This study supports the hypothesis that, just as for NC, NPP-FET may be a superior alternative to AC in terms of LBR. WHAT IS KNOWN ALREADY: Although FETs are increasing worldwide, the optimal FET protocol is still largely controversial. Despite recent evidence supporting a possibly higher efficacy and safety of NC FETs, their widespread use is limited by the difficulties encountered during cycle monitoring and scheduling. STUDY DESIGN, SIZE, DURATION: In this single center retrospective cohort study, we describe the NPP-FET protocol, in which vaginal progesterone is initiated during the proliferative phase as soon as an endometrium with a thickness of at least 7 mm is identified and ovulation is ruled out, regardless of mean diameter of the dominant follicle. PARTICIPANTS/MATERIALS, SETTING, METHODS: For comparison, we considered all blastocyst stage FET cycles preformed at a private infertility center between January 2010 and June 2022, subdivided according to the following subgroups of endometrial preparation: AC, NPP, and NC. We performed multivariable generalized estimating equations regression analysis to account for the following potential confounding variables: oocyte age at retrieval, oocyte source (autologous without preimplantation genetic testing for aneuploidies (PGT-A) versus autologous with PGT-A versus donated), number of oocytes retrieved/donated, embryo developmental stage (Day 5 versus Day 6), number of embryos transferred, quality of the best embryo transferred, and year of treatment. The main outcome measure was LBR. The secondary outcomes included hCG positive, clinical pregnancy and miscarriage rates, and the following perinatal outcomes: first trimester bleeding, second/third trimester bleeding, preterm rupture of membranes, gestational diabetes, gestational hypertensive disorders (GHD), and gestational age at delivery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 5791 FET cycles were included in this analysis (2226 AC, 349 NPP, and 3216 NC). The LBR for FET was lower in the AC subgroup when compared to the NPP and NC (38.4%, 49.1%, and 45.2%, respectively; P < 0.01 AC versus NPP and AC versus NC). The rates of miscarriage were also lower in the NPP and NC subgroups when compared to AC (19.7%, 25.0%, and 34.9%, respectively; P < 0.01 NPP versus AC and NC versus AC). Considering perinatal outcomes, NPP-FET and NC were associated with a significantly lower first trimester bleeding compared to AC (17.3%, 14.7%, and 37.6%, respectively; P < 0.01 NPP versus AC and NC versus AC). Additionally, NC was associated with a lower rate of GHD when compared with AC (8.6% versus 14.5%, P < 0.01), while the rate following NPP-FET was 9.4%. LIMITATIONS, REASONS FOR CAUTION: This study is limited by its retrospective design. Moreover, there was also a low number of patients in the NPP subgroup, which may have led the study to be underpowered to detect clinically relevant differences between the subgroups. WIDER IMPLICATIONS OF THE FINDINGS: Our study posits that the NPP-FET protocol may be an effective and safe alternative to both NC and AC, while still allowing for enhanced practicality in patient follow-up and FET scheduling. Further investigation on NPP-FET is warranted, with prospective studies including a larger and more homogeneous subsets of patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA-Lisbon (2008-LIS-053-CG). The authors did not receive any funding for this study. The authors have no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Avoiding weekend frozen embryo transfer in modified natural cycles: is it possible?

In this era of the freeze-all strategy, the prevalence of frozen embryo transfer (FET) cycles is increasing rapidly. Although still quite often used, the hormone replacement therapy cycle to prepare a FET should now belong to the past, unless strictly necessary. This raises questions about possible flexible protocols for the preparation of an FET cycle in a (modified) natural cycle. In this viewpoint, an overview of the different options is discussed, stressing the importance of the corpus luteum.

Añadir medicación oral a los ciclos de fiv en ciclo natural no aporta beneficio a los resultados clínicos / Adding oral medication does not have any benefit on natural-cycle ivf results

Introducción: En los últimos años, los tratamientos de FIV en ciclo natural y la FIV con estimulación ovárica “suave” están resurgiendo como una opción más segura, económica y cómoda para las pacien-tes. Definimos FIV en ciclo natural como el tratamiento en el que los ovocitos son obtenidos de un ciclo ovulatorio espontáneo. Cuando añadimos fármacos orales (citrato de clomifeno o letrozol), hablamos de estimulación “mínima”. El objetivo de este estudio es clarificar si la introducción de esta medicación es beneficiosa para las pacientes. Materials y métodos: Analizamos retrospectivamente los tratamientos de FIV en ciclo natural o con estimulación mínima llevados realizados en nuestro centro de enero 2016 a diciembre 2020.Resultados: Encontramos diferencias significativas entre los dos protocolos en el número de ovocitos obtenidos después de la punción folicular (1.03 vs 1.63, p<0.001), número de ovocitos maduros (0.9 vs 1.3, p < 0.01), ovocitos fecundados (0.7 vs 1.1, p < 0.01), y número de embriones disponibles para trans-ferencia (0.5 vs 0.7, p < 0.01). Sin embargo, no encontramos diferencias en la tasa de embarazo (26,3% vs 19,6%, p=0.251) ni en la tasa de recién nacido vivo (16.3% vs 14,3%, p=0.7806).Discusión: Añadir medicación oral a la FIV en ciclo natural no parece tener ningún impacto sobre los resultados clínicos del ciclo. Son necesarios más estudios, pero podríamos reconsiderar la necesidad de añadir esta medicación, ya que supone un mayor coste para los pacientes. (AU)

Introduction: In recent years, natural cycle IVF and minimal ovarian stimulation IVF had been under-going a revival, gaining recognition as safer, cheaper, and more comfortable options for patients. We define natural cicle IVF as the treatment in which oocytes are obtained from a spontaneous ovulatory cycle. When oral drugs are used (usually clomiphene citrate or letrozole), the process is referred to as minimal ovarian stimulation cycle IVF. The aim of this study is to clarify whether the introduction of oral medication is beneficial for patients.Methods: We retrospectively analysed all natural or minimal ovarian stimulation IVF treatments that took place in our clinic during the studied period (January 2016 - December 2020). Descriptive variables were analysed with a t-test, and a chi-square test was performed on result variables. Results: We found significant differences, between both protocols, in the number of oocytes obtained after oocyte retrieval (1.03 vs 1.63, p<0.001), number of mature oocytes (0.9 vs 1.3, p < 0.01), fertilized oocytes (0.7 vs 1.1, p < 0.01), and number of embryos available for transfer (0.5 vs 0.7, p < 0.01).Howe-ver, we did not found signficant differences in terms of pregnancy rate (26,3% vs 19,6%, p=0.251) or live birth rate (16.3% vs 14,3%, p=0.7806). (AU)

Natural Cycle Frozen Embryo Transfer: Evaluating Optimal Protocols for Preparation and Timing.

Background: While natural cycle frozen embryo transfer (NC-FET) is becoming increasingly common, significant practice variation exists in the use of ovulation induction medications, administration of ovulation trigger, and timing of embryo transfer without consensus as to the optimal protocol. Aims: The objective of this study is to evaluate the association of key aspects of the NC-FET protocol with implantation, pregnancy and live birth. Settings and Design: This was a retrospective cohort study of blastocyst stage NC-FET cycles from October 2019 to July 2021 at a single academic fertility centre. Materials and Methods: Protocols varied between cycles across three key parameters which were evaluated as primary predictors of cycle outcomes: (1) use of letrozole for mild ovarian stimulation/ovulation induction, (2) administration of exogenous ovulation trigger versus spontaneous luteinising hormone surge and (3) transfer timing based on ovulation trigger versus sequential progesterone monitoring. Primary outcomes included implantation rate, clinical pregnancy and ongoing pregnancy. Statistical Analysis Used: Generalised estimating equations were fitted to obtain adjusted odds ratios or rate ratios as appropriate with 95% confidence intervals for each outcome across the three primary predictors. Results: A total of 183 cycles from 170 unique patients were eligible for inclusion. The average implantation rate was 0.58, resulting in an overall clinical pregnancy and ongoing pregnancy rate of 59.0% and 51.4%, respectively. After adjusting for age at embryo freeze and history of a failed embryo transfer, there were no significant associations between any predictor and implantation rate, clinical pregnancy, ongoing pregnancy, or live birth. Conclusion: In NC-FET, a variety of preparation and timing protocols may lead to comparable cycle outcomes, potentially allowing for flexibility on the basis of patient and physician preference. These findings warrant validation in a larger, randomised trial.

Clinical Efficacy of Oral Dydrogesterone Alone in Natural Cycle Frozen-thawed Embryo Transfer / 中山大学学报(医学科学版)

ObjectiveTo investigate the clinical efficacy of oral dydrogesterone alone for luteal phase support in natural cycle frozen-thawed embryo transfer （NC-FET）. MethodsThe clinical data of 1 530 NC-FET cycles enrolled in our Reproductive Center from January 2019 to September 2021 were retrospectively analyzed. According to different luteal support protocols， the patients were divided into oral dydrogesterone alone （group A， n=524）， vaginal progesterone soft capsules （group B， n=401） and vaginal progesterone soft capsules combined with dydrogesterone （group C， n=605）. The clinical outcomes and cost-effectiveness ratio were compared among the three groups. The primary outcome was live birth rate. ResultsThe live birth rate was 43.13% （226/524） in group A， 39.15% （157/401） in group B， and 42.64% （258/605） in group C. There was no statistical difference among the three groups （P > 0.05）. No statistical difference was observed in the HCG positive rate， implantation rate， biochemical pregnancy rate， clinical pregnancy rate， spontaneous miscarriage rate， ectopic pregnancy rate， twin delivery rate， premature delivery rate and newborn weight among the three groups （P>0.05）. Logistic regression analysis revealed that the three luteal support regimens did not affect live birth rate. Pharmacoeconomic analysis showed that taking group B as a reference， the cost increased by 19 227.30 yuan for every 1% increase in live birth rate in group A. ConclusionsIn NC-FET cycle， oral dydrogesterone alone can achieve the same clinical outcomes as vaginal progesterone soft capsules and vaginal progesterone soft capsules combined with dydrogesterone. Compared with that of progesterone soft capsules， the cost of oral dydrogesterone alone is increased， a large sample and multicenter prospective study is needed to further confirm our results.

Fecundación in vitro (FIV) en ciclo natural: del origen de la FIV a la práctica asistencial actual / Natural cycle in vitro fertilization (IVF): from the origins of IVF to current healthcare practice

El principio básico de la fecundación in vitro en ciclo natural (FIV-CN) recae en el reclutamiento mediante la selección folicular espontánea, minimizando la manipulación del ciclo de la mujer. Recientemente esta técnica ha suscitado mayor interés y se han puesto en valor muchas de sus ventajas respecto a la FIV convencional (FIVc). FIV-CN y FIVc son tratamientos complementarios que permiten ampliar el espectro terapéutico en las parejas con indicación de FIV. La FIV-CN constituye un tratamiento a considerar especialmente en la paciente con mal pronóstico para la FIVc por baja reserva ovárica. La edad es su principal factor pronóstico y los resultados son aceptables hasta los 40 años. El principal factor limitante de la FIV-CN es el riesgo de cancelación por ovulación, que puede reducirse mediante diferentes estrategias. No obstante, los resultados por transferencia embrionaria son satisfactorios en diferentes series publicadas.

The basic principle of natural cycle in vitro fertilization (NC-IVF) lies in recruitment through spontaneous follicular selection, avoiding or minimizing the use of drugs and manipulation of the woman's cycle. In recent years, this technique has attracted growing interest and many of its advantages over conventional IVF (cIVF) have been highlighted. NC-IVF and cIVF should be considered complementary treatments, which broaden the therapeutic spectrum for couples for whom IVF is indicated. NC-IVF could be considered in patients with poor prognosis for cIVF due to low ovarian reserve. Age is the main prognostic factor and results are acceptable up to 40 years of age. The main limiting factor is the risk of cancellation due to ovulation, which can be reduced through different strategies. Pregnancy rate per embryo transfer results are encouraging.

Comparison of clinical pregnancy rates between two types of endometrial preparation protocols for patients with thin endometrium in frozen-thawed embryo transfer cycles / 中国实用妇科与产科杂志

OBJECTIVE: To compare the clinical pregnancy rates between two types of endometrial preparation protocolsnatural cycle（NC）and hormone replacement cycle（HRT）-in patients with thin endometrium in the frozen-thawed embryo transfer（FET）cycles.METHODS: From January 2012 to December 2018,FET patients with endometrial thickness ≤7 mm on the day of human chorionic gonadotropin（h CG）trigger in Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University were selected as research subjects.According to the endometrial preparation protocols,they were divided into NC group and HRT group.Totally 117 pairs were successfully matched using the propensity score matching method.The matching variables were age,embryo type and number of transferred embryos,and the embryo implantation rate and clinical pregnancy rate of the two matched groups were compared.RESULTS: There was no significant difference in embryo implantation rate（36.47% vs. 39.03%）or clinical pregnancy rate（44.40% vs. 52.10%）between NC group and HRT group（P> 0.05）.CONCLUSION: NC group and HRT group had similar pregnancy rate in patients with thin endometrium in FET cycles.Individualized protocols can be adopted according to the characteristics of patients with thin endometrium.

Human chorionic gonadotropin-administered natural cycle versus spontaneous ovulatory cycle in patients undergoing two pronuclear zygote frozen-thawed embryo transfer

OBJECTIVE: To compare human chorionic gonadotropin (HCG)-administered natural cycle with spontaneous ovulatory cycle in patients undergoing frozen-thawed embryo transfer (FTET) in natural cycles. METHODS: In this retrospective cohort study, we analyzed the clinical outcome of a total of 166 consecutive FTET cycles that were performed in either natural cycle controlled by HCG for ovulation triggering (HCG group, n=110) or natural cycle with spontaneous ovulation (control group, n=56) in 166 infertile patients between January 2009 and November 2013. RESULTS: There were no differences in patients' characteristics between the 2 groups. The numbers of oocytes retrieved, mature oocytes, fertilized oocytes, grade I or II embryos and frozen embryos in the previous in vitro fertilization (IVF) cycle in which embryos were frozen were comparable between the HCG and control groups. Significant differences were not also observed between the 2 groups in clinical pregnancy rate (CPR), embryo implantation rate, miscarriage rate, live birth rate and multiple CPR. However, the number of hospital visits for follicular monitoring was significantly fewer in the HCG group than in the control group (P < 0.001). CONCLUSION: Our results demonstrated that HCG administration for ovulation triggering in natural cycle reduces the number of hospital visits for follicular monitoring without any detrimental effect on FTET outcome when compared with spontaneous ovulatory cycles in infertile patients undergoing FTET in natural ovulatory cycles.

N-glycoproteomic analysis of human follicular fluid during natural and stimulated cycles in patients undergoing in vitro fertilization / 대한생식의학회지

OBJECTIVE: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry. METHODS: For profiling of the total proteome and glycoproteome, pooled protein samples from natural and stimulated hFF samples were selectively isolated using hydrazide chemistry to obtain the total proteomes and glycoproteomes. N-GPs were validated by the consensus sequence N-X-S/T (92.2% specificity for the N-glycomotif at p<0.05). All data were compared between natural versus hyperstimulated hFF samples. RESULTS: We detected 41 and 44 N-GPs in the natural and stimulated hFF samples, respectively. Importantly, we identified 11 N-GPs with greater than two-fold upregulation in stimulated hFF samples compared to natural hFF samples. We also validated the novel N-GPs thyroxine-binding globulin, vitamin D-binding protein, and complement proteins C3 and C9. CONCLUSION: We identified and classified N-GPs in hFF to improve our understanding of follicular physiology in patients requiring assisted reproduction. Our results provided important insights into the prevention of hyperstimulation side effects, such as OHSS.

Comparative study between natural cycles and programmed cycles using exogenous steroid hormones for endometrial preparation in cryopreserved-thawed blastocyst transfer / 대한산부인과학회지

OBJECTIVE: The objective of this study was to compare the outcomes of cryopreserved-thawed blastocyst transfer (CT-BT) in natural or programmed cycles using exogenous steroid hormones. METHODS: A total of 221 CT-BT cycles were included and divided into two groups according to endometrial preparation protocols. In natural cycle group (n=116), monitoring was performed by transvaginal ultrasonography to detect ovulation. In programmed cycle group (n=105), oral estradiol valerate, 6 mg/day, was started on the third day of the menstrual cycle and administered continuously, and progesterone in oil 100 mg i.m. daily injection was started on cycle day 15. CT-BTs were performed on five days after ovulation in natural cycles and five days after the initiation of progesterone administration in programmed cycles. Pregnancy rates, implantation rates, and other clinical characteristics of the two groups were compared. RESULTS: Clinical characteristics of study subjects did not differ between the two groups. Post-thaw survival rates, number of transferred blastocysts, and number of good-quality blastocysts were not different. There were no statistically significant differences in implantation rates (21.1% vs. 19.4%), clinical pregnancy rates (36.2% vs. 36.2%), and ongoing pregnancy rates (28.4% vs. 27.6%) between the two groups. CONCLUSIONS: No statistically significant differences were found in pregnancy rates and implantation rates between the two protocols. Our results suggest that both protocols are equally effective for endometrial preparation in CT-BT cycles.