Effect of ovarian stimulation on developmental speed of preimplantation embryo in a mouse model.

Ovarian stimulation protocols are widely used to collect oocytes in assisted reproductive technologies (ARTs). Although the influence of ovarian stimulation on embryo quality has been described, this issue remains controversial. Here, we analyzed the influence of ovarian stimulation on developmental speed and chromosome segregation using live cell imaging. Female mice at the proestrus stage were separated by the appearance of the vagina as the non-stimulation (-) group, and other mice were administered pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) as the stimulation (+) groups. The cumulus-oocyte complexes from both groups were inseminated with sperm suspensions from the same male mice. Fertilization rates and developmental capacities were examined, and the developmental speed and frequency of chromosome segregation errors were measured by live-cell imaging using a Histone H2B-mCherry probe. The number of fertilized oocytes obtained was 1.4-fold more frequent in the stimulation (+) group. The developmental rate and chromosome stability did not differ between the groups. Image analysis showed that the mean speed of development in the stimulation (+) group was slightly higher than that in the non-stimulation (-) group. This increase in speed seemed to arise from the slight shortening of the 2- and 4-cell stages and third division lengths and consequent synchronization of cleavage timing in each embryo, not from the emergence of an extremely rapidly developing subpopulation of embryos. In conclusion, ovarian stimulation does not necessarily affect embryo quality but rather increases the chances of obtaining high-quality oocytes in mice.

Anti-Müllerian hormone for screening, diagnosis, evaluation, and prediction: A systematic review and expert opinions.

AIM: To present evidence-based recommendations for anti-Müllerian hormone (AMH) measurement as an ovarian reserve test. METHODS: A systematic literature search for the clinical utility of AMH was conducted in PubMed from its inception to August 2022 to identify studies, including meta-analyses, reviews, randomized controlled trials, and clinical trials, followed by an additional systematic search using keywords. Based on this evidence, an expert panel developed clinical questions (CQs). RESULTS: A total of 1895 studies were identified and 95 articles were included to establish expert opinions subdivided into general population, infertility treatment, primary ovarian insufficiency, polycystic ovary syndrome, surgery, and oncofertility. We developed 13 CQs and 1 future research question with levels of evidence and recommendations. CONCLUSION: The findings of the current systematic review covered the clinical utility of AMH including its screening, diagnosis, evaluation, and prediction. Although some clinical implications of AMH remain debatable, these expert opinions may help promote a better understanding of AMH and establish its clinical significance.

Evolution of intracytoplasmic sperm injection: From initial challenges to wider applications.

Background: In vitro fertilization (IVF) has revolutionized infertility treatment. Nevertheless, male infertility requires more effective solutions. In 1992, the first-ever case of human birth via intracytoplasmic sperm injection (ICSI) was reported. ICSI involves microscopically injecting a sperm into an ovum. Successful ICSI has become a reliable therapy for couples facing infertility, a significant milestone. However, it has also introduced various challenges. This study also delves into ethical dilemmas arising from widespread ICSI use. Methods: This review traces the history of ICSI, presenting pioneering attempts, first successful attempts, and critical reports on account of the initial skepticism toward the technology. The review also focuses on chronological progress until ICSI was recognized as effective and became widely applied. Main findings: The review reveals that ICSI, although transformative, presents challenges. Successes include addressing male infertility and aiding fertilization. However, concerns arise regarding optimal sperm and embryo selection, genetic mutations, and long-term health implications. Ethical considerations surrounding ICSI's broad applications also surface. Conclusions: Despite its success and effectiveness, ICSI is still evolving as a therapeutic method. By comprehensively evaluating the historical progress and the current status of ICSI and exploring its future prospects, this study highlights the importance of ICSI in infertility treatment.

Beyond appearance: Can morphologically low-grade euploid blastocysts yield successful pregnancies?

Purpose: The primary objective of this investigation is to evaluate how morphological quality affects the pregnancy outcomes in euploid embryos determined by preimplantation genetic testing for aneuploidies (PGT-A). Concurrently, as a secondary objective, we aim to identify which specific aspects of morphological evaluation exert the most significant impact on these outcomes. Methods: A retrospective analysis of 451 single euploid embryo transfer cycles at our clinic was conducted. Embryos were evaluated based on the degree of blastocyst expansion, inner cell mass (ICM), trophectoderm (TE) morphology, and the day of blastocyst vitrification. Outcomes between morphologically low-grade and high-grade embryos were compared. Additionally, the study analyzed which morphological factors most influenced pregnancy outcomes. Results: Pregnancy outcomes were significantly lower in morphologically low-grade blastocysts compared to high-grade ones. Among the morphological evaluations, the ICM assessment was significantly associated with the live birth rate. Conclusion: Our study indicates that the morphological quality of euploid embryos, particularly the evaluation of the ICM, plays a crucial role in IVF-ET success.

Risk factors for non-previa placenta accreta spectrum in pregnancies conceived through frozen embryo transfer during a hormone replacement cycle in Japan.

Purpose: Non-previa placenta accreta spectrum (PAS) is associated with assisted reproductive technology (ART), particularly frozen embryo transfer during hormone replacement therapy (HRC-FET). We especially aimed to evaluate the prevalence and risk factors for non-previa PAS in HRC-FET pregnancies. Methods: Overall, 279 women who conceived through ART at three ART facilities and delivered at a single center were included in this retrospective study. Data regarding endometrial thickness at embryo transfer, previous histories, and type of embryo transfer-HRC-FET, frozen embryo transfer during a natural ovulatory cycle (NC-FET), and fresh embryo transfer (Fresh-ET)-were collected. Univariable logistic regression analyses were conducted. Results: The prevalence of non-previa PAS was 27/192 (14.1%) in the HRC-FET group and 0 (0.0%) in both the NC-FET and Fresh-ET groups. Significantly high odds ratio [95% confidence interval] of non-previa PAS was associated with a history of artificial abortion (6.45 [1.98-21.02]), endometrial thickness <8.0 mm (6.11 [1.06-35.12]), resolved low-lying placenta (5.73 [2.13-15.41]), multiparity (2.90 [1.26-6.69]), polycystic ovarian syndrome (2.62 [1.02-6.71]), and subchorionic hematoma (2.49 [1.03-6.04]). Conclusions: A history of artificial abortion, endometrial thickness <8.0 mm, and resolved low-lying placenta may help in antenatal detection of a high-risk population of non-previa PAS in HRC-FET pregnancies.

Development of an AI-based support system for controlled ovarian stimulation.

Purpose: Controlled ovarian stimulation (COS) is vital for IVF. We have developed an AI system to support the implementation of COS protocols in our clinical group. Methods: We developed two models as AI algorithms of the AI system. One was the oocyte retrieval decision model, to determine the timing of oocyte retrieval, and the other was the prescription inference model, to provide a prescription similar to that of an expert physician. Data was obtained from IVF treatment records from the In Vitro Fertilization (IVF) management system at the Asada Ladies Clinic, and these models were trained with this data. Results: The oocyte retrieval decision model achieved superior sensitivity and specificity with 0.964 area under the curve (AUC). The prescription inference model achieved an AUC value of 0.948. Four models, namely the hCG prediction model, the hMG prediction model, the Cetrorelix prediction model, and the Estradiol prediction model included in the prescription inference model, achieved AUC values of 0.914, 0.937, 0.966, and 0.976, respectively. Conclusion: The AI algorithm achieved high accuracy and was confirmed to be useful. The AI system has now been implemented as a COS tool in our clinical group for self-funded treatments.

Factors affecting the distribution of serum anti-müllerian hormone levels among infertile Asian women: a multi-nation, multi-centre, and multi-ethnicity prospective cohort study.

STUDY QUESTION: How do age, ethnicity, and other characteristics affect serum anti-mullerian hormone (AMH) levels in Asian women undergoing fertility treatment? SUMMARY ANSWER: Age, ethnicity, obesity (BMI ≥ 30 kg/m2), and polycystic ovarian syndrome (PCOS) significantly impacted serum AMH levels, with the rate of decrease accelerating as age increased; a concentration of 4.0 ng/ml was the optimal cut-off for diagnosis of PCOS. WHAT IS KNOWN ALREADY: There are significant differences in ovarian reserve among women from different races and ethnicities, and Asian women often have poorer reproductive outcomes during assisted reproductive treatment cycles. STUDY DESIGN, SIZE, DURATION: A population-based multi-nation, multi-centre, multi-ethnicity prospective cohort study of 4613 women was conducted from January 2020 to May 2021. Infertile women of 20-43 years of age were enrolled. The exclusion criteria included: age <20 or >43, non-Asian ethnicity, and missing critical data. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were Asian women of Chinese, Japanese, Korean, Thai, Vietnamese, Malay, Indian, and Indonesian ethnicities from 12 IVF centres across Asia. These women were all naïve to ovarian stimulation cycles and attended IVF centres for fertility assessment. The AMH measurement was performed using an AMH automated assay on a clinically validated platform. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 4556 infertile Asian women were included in the final analyses. The mean ± SD for serum AMH concentrations (ng/ml) across specific age groups were: overall, 3.44 ± 2.93; age <30, 4.58 ± 3.16; 30-31, 4.23 ± 3.23; 32-33, 3.90 ± 3.06; 34-35, 3.21 ± 2.65; 36-37, 2.74 ± 2.44; 38-39, 2.30 ± 1.91; 40 and above, 1.67 ± 2.00. The rate of AMH decrease was ∼0.13 ng/ml/year in patients aged 25-33 and 0.31 ng/ml/year in women aged 33-43. The highest rates of PCOS were found in Indians (18.6%), Malays (18.9%), and Vietnamese (17.7%). Age (P < 0.001), ethnicity (P < 0.001), obesity (P = 0.007), PCOS (P < 0.001), and a history of endometrioma cystectomy (P = 0.01) were significantly associated with serum AMH values. Smoking status, pretreatment with GnRH agonist (GnRHa) or the oral contraceptive pill (OCP), freezing-thawing of blood samples, and sampling on Day 2 to Day 5 of the menstrual cycle or randomly did not appear to affect serum AMH levels. An AMH concentration of 4.0 ng/ml was the optimal cut-off for PCOS diagnosis with a sensitivity of 71.7% and specificity of 75.8% (AUC = 0.81, CI 95%: 0.79-0.83; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The incidence of PCOS was supposedly high in this cohort as some IVF clinics were tertiary referral centres for managing specific fertility issues encountered by women with PCOS. Treatment with GnRHa or OCP before AMH testing was regionally and ethnically confined, mostly in Hong Kong SAR and Japan. Moreover, this reference for serum AMH value is limited to Asian women of the ethnicities examined and may not apply to other ethnicities not included in the study. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to collate and construct age-specific reference ranges for serum AMH levels using the same bioassay on Asian women of different ethnicities. The findings of this investigation can assist clinicians to counsel and prognosticate about Asian women's ovarian reserve and reproductive potential, thus providing better strategies for personalized fertility interventions. STUDY FUNDING/COMPETING INTEREST(S): This study was technically supported by Ferring Pharmaceuticals and received no specific grant from any funding agency. All authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: NCT04203355.

Cryptozoospermia: Should we use ejaculated sperm or surgically retrieved sperm for assisted reproductive technology?

Purpose: In cryptozoospermic subjects, it may often may be difficult to secure motile sperm for assisted reproductive technology (ART). We examined the results of ART with frozen thawed ejaculated sperm in cryptozoospermic subjects and evaluated whether sperm retrieval surgery is necessary for such patients in our clinic. Methods: Between 2013 and 2021, we evaluated 197 cryptozoospermic patients. Age, endocrine panel at the time of the initial semen analysis, and anti-müllerian hormone levels at the time of the spouse's first egg retrieval were examined. Cryopreservation of ejaculated motile sperm collected essentially weekly over a 3-month period was carried out. ART data recorded was the number of egg retrieval cycles, normal fertilization rate, and clinical pregnancy rate. Results: ART using frozen sperm as well as sperm ejaculated on the day of egg retrieval was possible in all cases. The normal fertilization rate was 70.4%, the clinical pregnancy rate per embryo transferred was achieved in 31.5% (870 cycles), and the live birth rate per case was 73.8%. Conclusions: Intracytoplasmic sperm injection (ICSI) was possible without sperm retrieval surgery in cryptozoospermia, resulting in 73.8% of live births per patient. Sperm identification, sperm processing, and ICSI technique are especially important in cryptozoospermia. Sperm retrieval surgery can be avoided in cryptozoospermic patients.

Risk factors for empty follicle syndrome in assisted reproductive technology with gonadotropin-releasing hormone agonist trigger.

Purpose: To analyze whether response to the GnRH test is a predictor of empty follicle syndrome (EFS) and to analyze independent risk factors for EFS. Methods: The GnRH test results of 3765 patients from 2016 to 2018 were used to define the reference range of the GnRH test. Risk factors for EFS were estimated by multivariate logistic analysis of 5282 cycles (5247 oocyte-retrieved cycles with GnRH agonist trigger and 35 cycles of EFS) conducted from 2016 to 2019. Results: GnRH testing showed basal hormone values as follows: median LH 5.2 (95 percentile; 1.3-12.6) mIU/mL, LH 30 min 22.0 (6.8-57.1), basal FSH 7.3 (3.0-20.5), FSH 30 min 11.5 (5.1-30.4) and FSH/LH ratio 1.5 (0.6-4.1). Independent risk factors for EFS were antral follicle count (adjusted odds ratio; 0.94, 95% CI; 0.89-0.99), basal LH (0.78, 0.66-0.90), and days duration of ovarian stimulation (1.41, 1.21-1. 60). The respective thresholds were 8 for AFC, 5.0 for basal LH, and 16 days for duration. Conclusions: LH 30 min values of the GnRH test did not predict EFS. Independent risk factors for EFS were AFC, basal LH and days duration of ovarian stimulation.

Clinical outcomes of personalized blastocyst embryo transfer after endometrial receptivity analysis: A multicenter, retrospective cohort study.

Purpose: To evaluate clinical outcomes after endometrial receptivity analysis (ERA). Methods: This was a multicenter, retrospective cohort study involving 861 women who underwent ERA testing at certified fertility clinics in Japan, and who received subsequent personalized blastocyst embryo transfers (ET) between 2018 and 2020. Clinical outcomes, including pregnancies, miscarriages, and live births, were evaluated according to receptivity status for ERA. Results: Mean patient age was 37.7 years (SD = 4.0), and the median number of previous ETs was 2 (interquartile range, 2-3). 41.0% (353/861) of patients were non-receptive for ERA testing. Clinical pregnancy, miscarriage, and live birth rates for personalized blastocyst ET were 44.5% (226/508), 26.1% (59/226), and 26.8% (136/508) for receptive patients, and 43.1% (152/353), 28.3% (43/152), and 28.9% (102/353) for non-receptive patients, all statistically nonsignificant. Multiple logistic regression demonstrated similar nonsignificant associations between receptivity and clinical outcomes. Greater patient age, smoking, and longer duration of infertility were significantly and negatively associated with receptivity, whereas a history of delivery was positively associated and statistically significant. Conclusions: Clinical outcomes after ERA testing were similar between receptive and non-receptive patients. Further prospective study including an appropriate comparison group are warranted to evaluate the efficacy of ERA testing.

Gonadotropin levels at the start of ovarian stimulation predict normal fertilization after hCG re-trigger in GnRH antagonist cycles.

PURPOSE: To assess the appropriateness of human chorionic gonadotropin (hCG) re-trigger in poor responders to gonadotropin-releasing hormone agonist (GnRHa) trigger in controlled ovarian stimulation (COS) cycles. METHODS: The 2251 cycles in 2251 patients triggered with GnRHa for oocyte stimulation, with or without requiring hCG re-trigger between 2013 and 2018, were retrospectively analyzed to compare gonadotropin levels at the start of COS and the rate of normal fertilization between the re-trigger and non-re-trigger group. Furthermore, patients in the re-trigger group were stratified by the rate of normal fertilization (good: ≥60% or poor: <60%) to compare patient demographics, hormone profiles, and clinical outcome between the subgroups. RESULTS: In the re-trigger group, FSH and LH levels at the start of COS were significantly lower in the good fertilization group than in the poor fertilization group (P < .01). Receiver operating characteristic curves identified cutoff values of the FSH and LH levels of 1.30 and 0.35 mIU/mL, respectively, for predicting ≥60% normal fertilization. CONCLUSION: Gonadotropin levels at the start of COS are predictors of response to GnRHa trigger and hCG re-trigger necessity, and may serve as indicators to help clinicians appropriately choose hCG re-trigger rather than abandoning the cycles or continuing the first oocyte aspiration attempt.

Development of an automated two pronuclei detection system on time-lapse embryo images using deep learning techniques.

PURPOSE: To establish an automated pronuclei determination system by analysis using deep learning technology which is able to effectively learn with limited amount of supervised data. METHODS: An algorithm was developed by explicitly incorporating human observation where the outline around pronuclei is being observed in determining the number of pronuclei. Supervised data were selected from the time-lapse images of 300 pronuclear stage embryos per class (total 900 embryos) clearly classified by embryologists as 0PN, 1PN, and 2PN. One-hundred embryos per class (a total of 300 embryos) were used for verification data. The verification data were evaluated for the performance of detection in the number of pronuclei by regarding the results consistent with the judgment of the embryologists as correct answers. RESULTS: The sensitivity rates of 0PN, 1PN, and 2PN were 99%, 82%, and 99%, respectively, and the overlapping 2PN being difficult to determine by microscopic observation alone could also be appropriately assessed. CONCLUSIONS: This study enabled the establishment of the automated pronuclei determination system with the precision almost equivalent to highly skilled embryologists.

Long-term outcomes of freeze-all strategy: A retrospective analysis from a single ART center in Japan.

PURPOSE: To demonstrate the benefits of the freeze-all strategy for in vitro fertilization treatment based on retrospective analyses. METHODS: Post-thaw embryo survival rates of slow-frozen embryos in 294 cycles and vitrified embryos in 12 195 cycles were assessed. Progesterone (P4) and estradiol (E2) levels per mature oocyte by age category were assessed in 9081 cycles and pregnancy rates with fresh embryo transfer and frozen-thawed embryo transfer by P4 level were assessed in 1535 cycles. RESULTS: The survival rates of frozen-thawed embryos were 92.5% with slow freezing and 99.1% with vitrification. P4 levels on the day of human chorionic gonadotropin (hCG) injection showed a trend toward an increase with age. The pregnancy rate per mature oocyte with fresh embryo transfer decreased dependently upon P4 level, while that with frozen-thawed embryo transfer was not affected by P4 level. The pregnancy rates with frozen-thawed embryo transfer were higher than those with fresh embryo transfer in patients aged 42 years or younger. CONCLUSIONS: The freeze-all strategy is a valuable treatment option which allows the separation of an embryo transfer cycle from an oocyte retrieval cycle, especially for patients with high P4 levels at oocyte retrieval and patients of advanced maternal age.

Clinical utility of chlormadinone acetate (Lutoral™) in frozen-thawed embryo transfer with hormone replacement.

PURPOSE: The clinical utility of chlormadinone acetate tablets (Lutoral™), an orally active progestin which has been available since June 2007, was compared to an in-house vaginal suppository formulation of progesterone used between 2006 and 2007 for assisted reproductive technology (ART). METHODS: We retrospectively evaluated the efficacy and safety of chlormadinone acetate by comparing the pregnancy rates and the incidences of birth defects and hypospadias in frozen-thawed embryo transfer cycles using the in-house vaginal progesterone and those using chlormadinone acetate for luteal phase support. RESULTS: The pregnancy rates in the frozen-thawed embryo transfer cycles were 31.2% (259/831) with vaginal progesterone for luteal phase support and 31.6% (4228/13 381) with chlormadinone acetate (no significant difference). In the cycles resulting in live birth following administration of chlormadinone acetate between July 2007 and December 2015, the incidence of birth defects was 2.8% (80/2893), and the incidence of hypospadias was 0.03% (1/2893). CONCLUSIONS: These results indicate that the pregnancy rate following frozen-thawed embryo transfer using chlormadinone acetate for luteal phase support was comparable with that using vaginal progesterone, with no increased risk of birth defects, including hypospadias, which has been a concern following the use of progestins.

Performance of anti-Müllerian hormone (AMH) levels measured by Beckman Coulter Access AMH assay to predict oocyte yield following controlled ovarian stimulation for in vitro fertilization.

PURPOSE: We evaluated the performance of anti-Müllerian hormone (AMH) measured by the Beckman Coulter fully automated Access assay to predict oocyte yield following controlled ovarian stimulation (COS) for in vitro fertilization (IVF). METHODS: The correlation between the Access assay and the pre-mixing method with Generation II ELISA assay (Gen II pre-mix assay) was assessed using 230 blood samples. The relationship of AMH level measured by the Access assay and the actual number of oocytes retrieved following COS was assessed using 3296 IVF cycles. The performances of AMH, follicle stimulating hormone (FSH), and estradiol (E2) in predicting the responses to COS were also evaluated by constructing receiver operating characteristic (ROC) curves. RESULTS: The AMH levels measured just before oocyte retrieval by the Access assay and the number of oocytes retrieved following COS showed a good correlation with R = 0.655. The ROC analysis revealed that the sensitivity of AMH was comparable with or lower than that of E2 but higher than that of FSH. CONCLUSIONS: With the improved Access AMH assays, AMH was as sensitive as E2 and could become an accurate marker of ovarian response to COS in more than 3000 Japanese IVF patients.

Superior clinical pregnancy rates after microsurgical epididymal sperm aspiration.

Purpose: To assess normal fertilization, clinical pregnancy, and live birth rates after the use of microscopic epididymal sperm aspiration (MESA). Methods: One-hundred-and-sixty azoospermic participants who underwent MESA were evaluated. The MESA was performed by using a micropuncture method with a micropipette. In cases in which motile sperm were not obtained after the MESA, conventional or micro-testicular sperm extraction (TESE) was completed. Results: Adequate motile sperm were retrieved in 71 participants by using MESA and in 59 out of 89 participants by using TESE. Of the total number of patients, 123 underwent intracytoplasmic sperm injection. After MESA, the normal fertilization rate was 73.5% and the clinical pregnancy rate per case was 95.7%. Healthy deliveries resulted after MESA in 65 (92.9%) cases and after TESE in 38 (71.7%) cases. Conclusion: The MESA specimen collection does not have any special requirements, such as mincing tissue disposition. The MESA also can reduce the amount of laboratory work that is needed for cryopreservation. In the authors' experience, MESA is a beneficial procedure and should be given priority over TESE.

Leydig cell tumor of the testis, presenting with azoospermia.

Case: A case of Leydig cell tumor, associated with azoospermia, is presented. Outcome: The levels of sex hormones obviously were decreased, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH), with elevated testosterone. Computed tomography revealed no adrenal gland tumor, but a significant calcification in the right scrotal content was observed. He received a right radical orchiectomy and then he was unable to ejaculate. An endocrine panel revealed significantly decreased levels of testosterone and the low LH level had remained. Hormone replacement therapy with combined LH and FSH successfully recovered and preserved spermatogenesis. Conclusions: Although the patient's sexual function deteriorated after surgery, hormone replacement therapy was successful in establishing spermatogenesis.

Age-specific serum anti-Müllerian hormone concentration in Japanese women and its usefulness as a predictor of the ovarian response.

Purpose: To compare the ovarian response predictive ability of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) and to determine the age-specific distribution of serum AMH concentrations of Japanese women. Methods: This was a multicenter (four-site), observational, analytic, cross-sectional Japanese study consisting of two parts: Study 1 (the prediction of the ovarian response of 236 participants who were undergoing controlled ovarian stimulation [COS]) and Study 2 (the distribution of the AMH concentration with an assay of 417 healthy women who were aged 20-49 years and who had normal menstrual cycles). Results: The AMH had a significantly higher predictive value for the normal and high responders than FSH and E2 as a stronger correlation between the ovarian response and AMH was observed than for FSH and E2. The serum AMH concentration decreased proportionally with age. Conclusion: The AMH concentration correlated well with the oocyte count in the patients who were undergoing COS for in vitro fertilization and was shown to predict the risk of ovarian hyperstimulation syndrome among these patients.

Perception and needs of reproductive specialists with regard to fertility preservation of young breast cancer patients.

BACKGROUND: Treatment-related infertility is one of the important quality-of-life issues in young breast cancer (YBC) patients. Although existing guidelines recommend supporting fertility preservation (FP) of YBC, the perceptions of reproductive specialists (RS) has not been evaluated. We investigated the perceptions and needs of RS with regard to FP of YBC patients. METHODS: A cross-sectional survey was sent to 423 certified RS registered to the Japan Society for Reproductive Medicine to self-evaluate their perceptions and needs regarding FP in YBC patients. RESULTS: Two hundred RS (47 %) responded to the survey. 99 % responded that RS should be engaged in FP of YBC patients. 88 % responded that they would like to treat YBC patients, while 46 % responded that cancer treatment is more important than childbirth, even when the patient is recurrence-free 5 years after primary treatment. Respondents affiliated to private clinics were more likely to accept both fertilized and unfertilized egg preservation than those affiliated with academic or general hospitals. 70 % responded that they were anxious about treating breast cancer patients: concerns regarding a greater or unknown risk of recurrence (66 %), insufficient knowledge about breast cancer (47 %), and lack of a patient's spouse/partner (24 %) were identified as major barriers in supporting FP for YBC patients. CONCLUSIONS: RS recognize the need for FP in YBC patients and are willing to participate in their care. Affiliation of RS was related to a positive attitude to egg preservation. Various concerns regarding FP among RS indicate the need for evidence that supports the safety of FP, inter-disciplinary communication, and practice guidelines.

Continuous high-dose estrogen controls serum FSH and LH levels: new treatment strategy for extremely low ovarian reserve patients, two case reports.

At present, there are no proven therapies to improve ovarian function in women with premature ovarian insufficiency (POI) or in those with extremely low ovarian reserve (LOR). We report successful IVF outcomes achieved with continuous high-dose estrogen supplementation in patients with LOR. Patients were 33- and 42-year-old nulligravidae with high-serum FSH (over 30 IU/L) and undetectable serum AMH (under 0.1 ng/mL) levels; however, neither patient fulfilled the diagnostic criteria for POI. After cycle cancellation and unsuccessful IVF treatment, both patients received conjugated estrogen (CE) supplementation (2.5-3.75 mg/day) from day 2 of their menstrual cycle to the day of HCG administration in their IVF treatment cycles. Following continuous high-dose estrogen supplementation, oocytes were successfully retrieved from both patients and fertilized. Both patients also achieved ongoing pregnancy through frozen-thawed embryo transfer cycles. In conclusion, high-dose estrogen supplementation down-regulated serum FSH and LH within their physiological ranges, which led to functional follicle growth and prevented early luteinization. Further studies will be needed to confirm the effect of this treatment on POI patients and to establish a new and individualized protocol for LOR patients.