Fiber-cavity ring-down temperature sensor using a transmissive configuration combined with the heterodyne detection technique.

A fiber Bragg grating temperature sensor based on the cavity ring-down technique is reported. A quasi-linear fiber cavity is proposed to reduce optical loss in the cavity instead of a conventional fiber-loop configuration. The heterodyne detection technique is applied to sensitively detect weak pulses from the cavity. A combination of the quasi-linear fiber cavity and heterodyne detection allows the sensitive detection of the decaying pulse trains and high-resolution measurement of the wavelength shift of the Bragg grating induced by the temperature change. A temperature resolution of about 0.01°C is achieved.

Assessment of embryologist sufficiency and associated regional disparities in Japanese assisted reproduction facilities using nationwide survey data (IZANAMI project).

AIMS: This study aims to comprehensively examine the employment and practices of embryologists in Japan's assisted reproductive technology (ART) laboratories, focusing on the impact of various factors such as ART cycle numbers, add-ons, and regional differences. Additionally, it seeks to assess the extent to which Japanese ART facilities meet international minimum standards set by the American Society for Reproductive Medicine (ASRM). METHODS: A survey was conducted from December 2021 to February 2022 among 621 ART facilities in Japan. The study categorized facilities into five ART cycle groups and compared the number of embryologists across these groups. It also examined the correlation between the number of embryologists, ART cycles, add-ons, and regional differences. Data were analyzed using linear regression and multiple linear regression analyses. RESULTS: The study's findings revealed a significant correlation between the total number of embryologists at each facility and the ART cycles. Notably, there were significant differences in the number of embryologists across all ART cycle categories. Of the 435 facilities, only 44.6% met the ASRM minimum embryologist staffing requirement. The regression analysis further highlighted the significance of ART cycles and preimplantation genetic testing for aneuploidies as factors. Moreover, the number of embryologists stationed at urban facilities was significantly higher than at nonurban facilities, indicating a potential regional disparity. CONCLUSION: In Japan, it was first found that more than 50% of ART facilities do not have sufficient embryologists in place relative to the number of ART cycles. Furthermore, the add-ons and regional differences affect the placement of embryologists.

A review of the optimization of thyroid function, thrombophilia, immunity and uterine milieu treatment strategy for recurrent implantation failure and recurrent pregnancy loss.

Background: Aside from embryonic factors, various factors can intricately interfere with embryo implantation and maintenance of pregnancy, causing recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL). This review focuses the optimization of thyroid function, thrombophilia, immunity, and uterine milieu (OPTIMUM) treatment strategy on RIF and RPL. Methods: Three studies employing the OPTIMUM treatment strategy for patients with RIF and/or RPL were reviewed. Results: The OPTIMUM improved pregnancy rates in women with RIF aged <40 years. Among advanced age women, however, no significant differences in pregnancy rates were observed between the control, OPTIMUM, and preimplantation genetic testing for aneuploidy (PGT-A) groups, although pregnancy rates were highest after OPTIMUM + PGT-A. The OPTIMUM reduced miscarriage rates in women with RPL aged <40 years. Among advanced age women, PGT-A, but not the OPTIMUM, contributed to miscarriage prevention. Factors predicting pregnancy success in women with RIF who received the OPTIMUM included thrombophilia and young age. Risk factors for an unsuccessful live birth among women with RPL who received the OPTIMUM included advanced age, infertility, diminished ovarian reserve, and non-ART treatment. Conclusions: The OPTIMUM can improve pregnancy outcomes in women with RIF/RPL, except for advanced age women with embryonic factor-induced reproductive failure.

Management strategies following implantation failure of euploid embryos.

Background: Euploid blastocyst implantation failure may result from embryonic factors undetectable by preimplantation genetic testing for aneuploidy (PGT-A); however, various nonembryonic factors can also intricately interfere with implantation. This review seeks to clarify evidence-based testing and treatments for implantation failure after euploid embryo transfer. Methods: We conducted a review of the literature on implantation failure after euploid embryo transfer or multiple embryo transfer cycles, which mainly included systematic reviews and meta-analyses. Results: The recommended tests for implantation failure include (1) hysteroscopy, (2) endometrial CD138 immunohistochemistry and bacterial culture, (3) serum 25-hydroxyvitamin D3, and (4) thrombophilia screening. Based on diagnostic findings, the following treatments have been recommended: (1) antibiotics for chronic endometritis, (2) vitamin D replacement, (3) lifestyle modification, and (4) low-dose aspirin starting from the postimplantation period for thrombophilia. Moreover, frozen-thawed single euploid blastocyst transfer using assisted hatching and hyaluronan-enriched transfer medium may support embryo implantation. Conclusion: To ensure a successful pregnancy in subsequent embryo transfers, simple, inexpensive, and evidence-based tests and treatments should be selected.

Performance evaluation of a time-division multiplexed fiber Bragg grating sensor based on heterodyne detection.

Using a technique to observe reflection spectra, the signal-to-noise ratio can be improved for time-division multiplexed interrogation of three fiber Bragg gratings (FBGs) based on heterodyne detection methods. To calculate peak reflection wavelengths of the FBG reflections, absorption lines of 12 C 2 H 2 are used as wavelength markers, and temperature dependence of the peak wavelength is measured for one FBG. Positioning the FBGs at a distance of 20 km from the control port demonstrates the applicability of this method to a long sensor network.

Fact-finding survey on assisted reproductive technology in Japan.

AIMS: In anticipation of the future development of assisted reproductive technology (ART) and to smoothly introduce new technology, it is necessary to understand the current staffing status of the medical system and the current state of treatment, as well as the status of in vitro fertilization add-ons, where the need for insurance coverage is currently a matter of debate. METHODS: ART facilities in Japan were surveyed (437 valid responses, response rate: 71%). Current staffing status of the medical system, implementation rates of ART, add-on treatments, and medical supplies were investigated. RESULTS: Despite the abundance of embryologists, nurses, and obstetricians and gynecologists in facilities, the majority of facilities lacked counselors, anesthesiologists, and other essential medical professionals. Conventional ovarian stimulation was widely adopted (median 120 [interquartile range 60-300] cycles), followed by mild ovarian simulation (60 [30-200]). Additionally, freeze-thaw embryo transfer cycles (300 [120-750]) were performed more frequently than fresh embryo transfer cycles (30 [30-60]). Among the add-ons, assisted hatching (85.1%), chronic endometritis examination (77.2%) and treatment (76.9%), artificial oocyte activation (67.3%), endometrial receptivity analysis (64.2%), and endometrial microbiome analysis (58.9%) were relatively widely employed. CONCLUSIONS: The implementation of frozen-thawed embryo transfer cycles, freeze-all strategies, and add-on treatments have become popular and widely accepted despite the lack of robust evidence regarding their safety and efficacy.

Hyaluronan-enriched transfer medium (HETM) can improve the implantation rate in morphologically poor euploid blastocyst transfer.

PURPOSE: Hyaluronan-enriched transfer medium (HETM) could improve the clinical pregnancy rate (CPR) for patients with repeated implantation failures (RIF). In contrast, there have been seldom reports addressing the potentially beneficial effects of HETM for morphologically poor blastocysts (MPBLs). Our study aimed to evaluate whether the use of HETM would improve the CPR for the patients who were transferred with euploid MPBLs. METHODS: Patients who underwent single euploid blastocyst transfer between July 2020 and June 2022 were enrolled. We included only those blastocysts confirmed as euploid by PGT-A, and those blastocysts were transferred after thawing. The natural ovulatory cycle or hormone replacement cycle (HRC) protocol were used for endometrial preparation for frozen embryo transfer (FET). A total of 1,168 FET cycles were performed in the study period, including 954 cycles of morphologically good blastocysts (≥ 4BB in Gardner's classification), and 85 cycles of MPBLs, of which 47 were transferred using HETM in FET (the HETM group), and the remaining 38 were transferred with the medium without hyaluronan (the control group). We compared the CPR between these two groups. RESULTS: The characteristics of patients were similar between the HETM and control groups. The CPR in the HETM group was significantly higher than the control group (47.4% and 21.5%, respectively, p = 0.019). The multiple logistic regression analysis found that the use of HETM was a predictive factor of positive pregnancy outcomes (OR = 5.08, 95% CI = 1.62-16.0, p = 0.019). CONCLUSION: Our data suggests that HETM used in the euploid blastocyst transfer can improve the clinical pregnancy rates of morphologically poor blastocysts.

Transcriptomic profiling analysis of human endometrial stromal cells treated with autologous platelet-rich plasma.

Purpose: To clarify the mechanisms of intrauterine platelet-rich plasma (PRP) infusion that support embryo implantation in in vitro fertilization treatment. Methods: Blood and endometrial samples were collected from four infertile women. Human endometrial stromal cells (HESCs) were cultured and passaged equally into four cell culture dishes in each patient. Two were treated with PRP twice, and the other two were treated with vehicle. Subsequently, two cultures with and without PRP were decidualized with 8-bromoadenosine 3',5'-cyclic AMP and progesterone for 5 days. Results: The gene expression in undifferentiated or decidualized HESCs with and without PRP was compared. In the microarray analysis, 381 and 63 differentially expressed genes were detected in undifferentiated and decidualized HESCs, respectively. In the undifferentiated HESCs, PRP was found to promote the gene expression associated with cell growth, tissue regeneration, proinflammatory response, and antibiotic effects. In decidualized HESCs, PRP was found to attenuate the gene expression involved in cell proliferation and inflammation by inhibiting the expression of phosphoinositide 3-kinase signaling. Conclusions: Platelet-rich plasma regulates the reprogramming of cell proliferation and inflammation depending on menstrual cycle phases in an appropriate manner, suggesting that PRP has the potential to increase endometrial thickness in the proliferative phase and improve immune tolerance in the secretory phase.

Therapeutic efficacy of gentle endometrial curettage on antibiotic-resistant chronic endometritis in infertile women.

Purpose: To identify the efficacy of endometrial curettage on antibiotic-resistant chronic endometritis (CE) in infertile women. Methods: Of 1580 women with CE, 87 with antibiotic-resistant CE after two to five cycles of antibiotic treatment were recruited between 2019 and 2021. The women who underwent endometrial curettage without applying any force and, in the subsequent menstrual cycle, endometrial sampling for CD138 immunostaining without antibiotic use. Pregnancy outcomes after in vitro fertilization treatment were analyzed in women who did not desire endometrial curettage and in those with cured and persistent CE after endometrial curettage. Results: In 64 women who underwent endometrial curettage, the number of CD138-positive cells decreased from 28.0 ± 35.3 to 7.7 ± 14.0 (p < 0.0001), and CE in 41 women (64.1%) was cured (<5 CD138-positive cells). The pathological findings detected 3.1% of endometrial hyperplasia and 1.6% of endometrial cancer. The ongoing pregnancy rates in women aged ≤42 without endometrial curettage were significantly lower than those of women with cured and persistent CE (26.7%, 67.6%, and 57.1%, respectively, p = 0.03). Conclusions: Gentle endometrial curettage for antibiotic-resistant CE significantly decreased the number of CD138-positive cells, resulting in improved pregnancy outcomes regardless of remaining CE. Endometrial curettage is also important as a screening for endometrial malignancy.

Therapeutic efficacy of the optimization of thyroid function, thrombophilia, immunity and uterine milieu (OPTIMUM) treatment strategy on pregnancy outcomes after single euploid blastocyst transfer in advanced age women with recurrent reproductive failure.

Purpose: To clarify the efficacy of the OPtimization of Thyroid function, Thrombophilia, IMmunity and Uterine Milieu (OPTIMUM) treatment strategy on pregnancy outcomes after euploid blastocyst transfer in advanced age women with recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL). Methods: Between January 2019 and May 2022, 193 consecutive women aged ≥40 years with RIF and/or RPL received single euploid blastocyst transfer. Before embryo transfer, 127 women underwent RIF/RPL testing. Chronic endometritis was treated with mainly antibiotics, aberrant high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. We compared pregnancy outcomes in the women who did and did not receive the OPTIMUM treatment strategy. Results: Women with RIF/RPL in the OPTIMUM group had significantly higher clinical pregnancy and livebirth rates than did those in the control group (clinical pregnancy rate of 71.7% and 45.5%, p < 0.001; livebirth rate of 64.6% and 39.4%, p = 0.001, respectively). However, preimplantation genetic testing for aneuploidy with and without OPTIMUM promoted low miscarriage rates with no significant difference between them (9.9%, and 13.3%, respectively; p = 0.73). Conclusions: The OPTIMUM treatment strategy improved clinical pregnancy rates after single euploid blastocyst transfer; but not miscarriage rates.

Risk factors for infertility treatment-associated harassment among working women: a Japan-Female Employment and Mental health in assisted reproductive technology (J-FEMA) study.

PURPOSE: This study aims to elucidate the risk factors of infertility treatment-associated harassment (I-harassment) among Japanese working women. METHODS: The study participants were 1103 female patients who enrolled in the Japan-Female Employment and Mental Health in artificial reproductive technology (J-FEMA) study. Of the 1727 female patients, 1103 female patients were working during the initiation of infertility treatment and were still working during the survey. Risk factors for I-harassment were analyzed using a multivariable logistic regression model. RESULTS: In this study, 82 female patients (7.4%) experienced I-harassment. The risk was significantly higher in those who had more in vitro fertilization (IVF) cycles than those who had fewer IVF cycles (OR, 1.06; 95% CI, 1.01-1.10). Similarly, those who disclosed their infertility treatment to their workplace were at significantly higher risk for I-harassment than those who did not (OR, 1.80; 95% CI, 1.03-3.15). CONCLUSION: This study found that 7.4% of female patients experienced I-harassment after infertility treatment initiation. Those female patients who "experienced more IVF cycles," and "disclosed their infertility treatment in their workplace" should be carefully followed up by healthcare professionals to prevent I-harassment.

Optimal individualization of patient-oriented ovarian stimulation in Japanese assisted reproductive technology clinics, a review for unique setting with advanced-age patients.

Ovarian stimulation is a key issue in assisted reproductive technology (ART) treatment. ART practice in Japan is unique with various types of ovarian stimulation protocols, which may contribute to lower pregnancy rates compared to other countries. This review aims to clarify optimal individualized ovarian stimulation for improving the pregnancy rate per one oocyte retrieval cycle in Japan. We performed a literature review to describe ovarian stimulation, classification of infertile women depending on ovarian reserve and response, and Japanese ART data and discussed optimal conventional and mild ovarian stimulation protocols in Japan. According to Japanese ART registry data, the live birth rate of 30-35-year-old women was 32%-37% per ET cycle; therefore, four to five embryos are calculatedly needed when aiming a cumulative live birth rate of ≥80%. Mild stimulation aimed at collecting 5-10 oocytes can be alternative choice as an optimal ovarian stimulation protocol in young women. In 40-year-old women, the live birth rate is 18.8%, resulting in eight or more embryos as necessary. Conventional stimulation must be required in women with advanced age. In poor responders, however, mild stimulation may be sufficient for maximumly extracting their ovarian function. In Japan, mild ovarian stimulation can be selected in patients with a good prognosis and poor responders; however, conventional ovarian stimulation is necessary for women in advanced age.

Therapeutic effects of an oral gonadotropin-releasing hormone receptor antagonist, relugolix, on preventing premature ovulation in mild ovarian stimulation for IVF.

PURPOSE: Can relugolix, a novel oral gonadotropin-releasing hormone receptor (GnRH) antagonist, function as an alternative ovulation inhibitor to GnRH antagonist injections? METHODS: This single-center, cross-sectional retrospective study compared premature ovulation rates and clinical outcomes in IVF treatment after mild ovarian stimulation with 40 mg of relugolix (relugolix group) or 0.25-mg injections of ganirelix acetate or cetrorelix acetate (injection group) between March 2019 and January 2020. Of 247 infertile women (256 IVF cycles) aged ≤42 years, 223 women (230 cycles) were evaluated. In the relugolix and injection groups, we compared 104 and 85 cycles after GnRH antagonist use before the LH surge (LH levels <10 mIU/ml) and 22 and 19 cycles during the LH surge (LH levels ≥10 mIU/ml), respectively. RESULTS: Before the LH surge, the ovulation rates in the two groups were very low (p = 0.838), however; during the LH surge, the cycles using relugolix had a high ovulation rate of 40.9% compared with no ovulation in the injection group (p = 0.002). There were no significant differences in embryo culture findings and pregnancy outcomes between the two groups. CONCLUSIONS: Although relugolix had a high ovulation suppressive effect, when the LH surge occurred, its effect was insufficient.

Heterodyne detection applied to a fiber Bragg grating-based sensor using a directly modulated distributed feedback laser.

The heterodyne detection technique is applied to a fiber Bragg grating (FBG)-based sensor. Specifically, a directly modulated distributed feedback laser array is used as a frequency scanning light source. Weak reflections from the FBG are recorded as a beat signal with a high signal-to-noise ratio using heterodyne detection. A reflection signal is clearly observed from the FBG with a reflectivity of 1% located at 60 km from the detection port.

Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals.

RESEARCH QUESTION: What are the risk factors affecting the incidences of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and severe hemoperitoneum in assisted reproductive technology (ART) treatment cycles? DESIGN: A retrospective cohort study was conducted on 1,435,108 oocyte retrieval cycles among Japanese ART registry data between 2007 and 2015. The study included 11,378 cycles with moderate-to-severe OHSS, 1182 cycles with severe hemoperitoneum, including 27 cycles with both conditions, and 1,422,575 cycles without moderate-to-severe OHSS and severe hemoperitoneum. RESULTS: The incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08%, respectively, and decreased by 0.57-fold and 0.29-fold from 2007 to 2015, respectively. In cycles with OHSS and cycles with hemoperitoneum women were younger (odds ratios [OR] 0.91 and 0.95, respectively) and had more retrieved oocytes (OR 1.09 and 1.01, respectively) compared with cycles without both complications. The use of a gonadotrophin-releasing hormone (GnRH) agonist protocol for ovarian stimulation was the highest risk factor in cycles with OHSS and hemoperitoneum (OR 1.83 and 1.24, respectively), followed by GnRH antagonist protocol (reference), gonadotrophin with or without oral medicine (OR 0.45 and 0.56, respectively) and natural or oral medicine (OR 0.02 and 0.19, respectively). In fresh embryo transfer, clinical pregnancy was associated with an increased risk of OHSS and hemoperitoneum (OR 1.19 and 2.34, respectively). CONCLUSIONS: The highest risk factors affecting OHSS and hemoperitoneum were the use of a GnRH agonist protocol and clinical pregnancy following fresh embryo transfer. The incidences of OHSS and hemoperitoneum have decreased yearly with a reduction of GnRH agonist use and fresh embryo transfer.

Effect of thyroxine treatment on pregnancy outcomes in infertile Japanese women with TSH levels between 2.5 µIU/mL and the upper reference limit: a retrospective study.

Recent randomized controlled studies have revealed that levothyroxine (LT4) treatment improves pregnancy outcomes only in infertile women with subclinical hypothyroidism who have thyroid autoantibodies (TAs), but not for those with high TSH levels within the normal range who have TAs. Here, we retrospectively investigated pregnancy outcomes in infertile Japanese women with 2.5 µIU/mL ≤ TSH < upper reference limit (URL). Between 2012 and 2018, 286 patients diagnosed with infertility were followed for more than 1 year at our institution. Among them, we included 106 patients with 2.5 µIU/mL ≤ TSH < URL. We divided these patients into four groups based on the combination of TA positivity and LT4 treatment status to assess the effects of LT4 treatment considering TA positivity on the incidence of pregnancy or miscarriage. In this study, we did not find any significant differences in the rates of pregnancy or miscarriage among the four groups (p = 0.81 and 0.52, respectively). In addition, logistic regression analysis showed that age and history of miscarriage were associated with the incidence of pregnancy, but presence of TAs and LT4 treatment status were not and that no variables examined were associated with the incidence of miscarriage. In summary, we were not able to demonstrate the benefit of LT4 treatment for pregnancy outcomes in Japanese euthyroid infertile women with 2.5 µIU/mL ≤ TSH < URL regardless of TA status in this study.

Analysis of severe psychological stressors in women during fertility treatment: Japan-Female Employment and Mental health in Assisted reproductive technology (J-FEMA) study.

PURPOSE: To identify risk factors for severe psychological stress in women undergoing fertility treatment. METHODS: This cross-sectional, multi-center study was conducted from August to December 2018. We recruited 1672 subjects who completed an anonymous, self-reported questionnaire regarding fertility treatment, conditions at work and home, and psychological stress using K6 score, which estimates psychological distress during the previous 30 days. We further focused our analysis on 1335 subjects who were working when starting fertility treatment. RESULTS: Of 1672 women, mean K6 score (range 0-24) was 4.8 ± 4.4, including 103 women (6.2%) with K6 score ≥ 13 (high K6), and classified as probable severe psychological distress. Multivariate logistic regression analysis showed that high K6 was strongly associated with low annual family income of ≤ USD55,700 (JPY6 million) (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.04-3.42), infertility duration of ≥ 2 years (OR 1.87, 95% CI 1.08-3.25), and no experience of childbirth (OR 2.04, 95% CI 1.05-3.97). Focusing on 1335 working women, 266 (19.9%) experienced resignation from work. High K6 was strongly associated with low family income (OR 2.83, 95% CI 1.52-5.28), cessation of professional duties (OR 2.08, 95% CI 1.05-4.14), infertility-related harassment in the workplace (OR 2.07, 95% CI 1.08-3.98), and perceived difficulties to continue working during fertility treatment (OR 2.94, 95% CI 1.15-7.50). CONCLUSION: Severe psychological stressors in women during fertility treatment included low family income, long infertility duration, childlessness, infertility-related harassment, and perceived difficulty in working conditions or cessation from work. Establishment of mental health care support systems is urgently required in this population.

Novel approaches to the management of recurrent pregnancy loss: The OPTIMUM (OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu) treatment strategy.

PURPOSE: Does the OPtimization of Thyroid function, Thrombophilia, Immunity, and Uterine Milieu (OPTIMUM) treatment strategy, developed for treating repeated implantation failure (RIF), contribute to improving pregnancy outcomes in patients with a history of recurrent pregnancy loss (RPL)? METHODS: Between 2018 and 2019, women with RPL after two or more clinical pregnancy losses underwent RPL testing. We treated chronic endometritis with antibiotics, high Th1/Th2 cell ratios with vitamin D and/or tacrolimus, overt/subclinical hypothyroidism with levothyroxine, and thrombophilia with low-dose aspirin. Of 168 consecutive women aged ≤43 years, 115 underwent RPL testing. We compared 100 pregnancies (90 women) and 46 pregnancies (41 women) with and without the OPTIMUM treatment strategy, respectively. RESULTS: RPL testing identified intrauterine abnormalities in 66 (57.4%), elevated Th1/Th2 cell ratios in 50 (43.5%), thyroid dysfunction in 33 (28.7%), and thrombophilia in 33 (28.7%). The live birth rate in the OPTIMUM group was significantly higher than that in the control group among women aged <40 years (78.1% and 42.3%, respectively; p = 0.002), but no significant difference was observed in women aged ≥40 years (55.6% and 30.0%, respectively; p = 0.09). CONCLUSIONS: The OPTIMUM treatment strategy improved pregnancy outcomes in patients with not only RIF but also RPL.

Analysis of vaginal and endometrial microbiota communities in infertile women with a history of repeated implantation failure.

PURPOSE: To identify specific bacterial communities in vaginal and endometrial microbiotas as biomarkers of implantation failure by comprehensively analyzing their microbiotas using next-generation sequencing. METHODS: We investigated α- and ß-diversities of vaginal and endometrial microbiotas using 16S rRNA gene sequencing and compared their profiles between 145 women with repeated implantation failure (RIF) and 21 controls who lacked the factors responsible for implantation failure with a high probability of being healthy and fertile to identify specific bacteria that induce implantation failure. RESULTS: The endometrial microbiotas had higher α-diversities than did the vaginal microbiotas (P < .001). The microbiota profiles showed that vaginal and endometrial samples in RIF patients had significantly higher levels of 5 and 14 bacterial genera, respectively, than those in controls. Vaginal Lactobacillus rates in RIF patients were significantly lower at 76.4 ± 38.9% compared with those of the controls at 91.8 ± 22.7% (P = .018), but endometrial Lactobacillus rates did not significantly differ between the RIF patients and controls (56.2 ± 36.4% and 58.8 ± 37.0%, respectively, P = .79). CONCLUSIONS: Impaired microbiota communities containing specific bacteria in both the endometrium and vagina were associated with implantation failure. The vaginal Lactobacillus rates, but not the endometrial, may be a biomarker for RIF.

The actions of resveratrol in decidualizing endometrium: acceleration or inhibition?†.

Resveratrol, a natural polyphenolic compound, is widely studied for its anti-inflammatory and antisenescent properties. Recently, two studies reported seemingly conflicting findings on the actions of resveratrol on decidualization of human endometrial stromal cells (HESCs). One study by Ochiai et al. demonstrated that resveratrol inhibits decidual transformation of primary cultured HESCs. The other study by Mestre Citrinovitz et al., showed that resveratrol enhances decidualization of HESCs in culture. At a glance, the reason for these opposing observations seems puzzling. However, recent studies demonstrated that decidualization is a multistep process, which starts with an acute proinflammatory stress response that lasts for several days and is followed by the emergence of stress-resistant decidual cells as well as senescent decidual cells. The balance between these decidual subpopulations may determine if the cycling endometrium can successfully transition into the decidua of pregnancy upon embryo implantation. Here, we explore the importance of timing of drugs aimed at modulating the decidual response. We posit that resveratrol treatment during the initial proinflammatory decidual phase, i.e., coinciding with the implantation window in vivo, inhibits decidual transformation of the endometrium. However, when given after the initial phase, resveratrol may promote decidualization by inhibiting decidual senescence. Further, if restricted to the proliferative phase, resveratrol may promote ovarian function without adversely impacting on embryo implantation or decidualization. Thus, failure to align drug interventions with the correct phase of the menstrual cycle may negate beneficial clinical effects and results in adverse reproductive outcomes.