The addition of dydrogesterone improves the outcomes of pregnant women with low progesterone levels when receiving vaginal progesterone alone as luteal support in HRT-FET cycles.

Purpose: Vaginal progesterone (VP) alone has been used as luteal support (LS) in HRT-FET cycles without measuring serum progesterone concentrations (SPC) because it can achieve adequate intrauterine progesterone levels. However, several reports showed that the co-administration of progestin produced better outcomes than VP alone. We tried to address this discrepancy, focusing on SPC. Methods: VP was given to 180 women undergoing HRT-FET. We measured SPC when pregnancy was diagnosed on day 14 of LS. We compared assisted reproductive technology outcomes between VP alone versus VP + dydrogesterone (D). Results: When using VP alone, average SPC in the miscarriage cases (9.6 ng/mL) were significantly lower compared with the ongoing pregnancy (OP) cases (14.7 ng/mL). The cut-off value for progesterone, 10.7 ng/mL, was a good predictor for the subsequent course of the pregnancy. Of 76 women receiving D ± VP from the start of LS and achieving a pregnancy, the numbers of OP were 44 (84.6%) in SPC ≥ 10.7 ng/mL and 20 (83.3%) in SPC ≤ 10.7 ng/mL with no significant difference. Conclusion: VP alone resulted in lower SPC in some pregnant women in HRT-FET cycles and exhibited a lower OP rate. The co-administration of D improved an OP rate of low progesterone cases to the level comparable with non-low progesterone cases.

A novel orally active gonadotropin-releasing hormone antagonist, relugolix, is a potential substitute for injectable GnRH antagonists in controlled ovarian stimulation in assisted reproductive technology.

PURPOSE: To evaluate the efficacy of an oral gonadotropin-releasing hormone antagonist (GnRH Ant), relugolix (R), for assisted reproductive technology (ART). METHODS: We enrolled women undergoing ART using a GnRH Ant for controlled ovarian stimulation. We compared R; 20 mg/day with cetrorelix acetate (C); 0.125 mg. C was administered to 88 women in 2019, and R to 93 women in 2020. Clinical outcomes associated with ART were assessed in both groups. RESULTS: The luteinizing hormone levels on the day of human chorionic gonadotropin injection in the R group (1.26 ± 0.93 IU/L) were significantly lower than those in the C group (2.85 ± 3.02 IU/L). There were no cases in which egg retrieval was canceled in both groups. The total doses of gonadotropins administered were greater in the R group compared with the C group. The number of days of GnRH Ant administration in the R group (1.71 ± 0.57 days) was significantly longer compared with the C group (1.48 ± 0.58 days). The number of oocytes collected, fertilization rates, and pregnancy rates (R; 47.1% vs C; 45.8%) did not differ between the two groups. CONCLUSION: An orally active GnRH Ant, relugolix, when used in controlled ovarian stimulation for ART, showed comparable clinical outcomes with cetrorelix.

Different anti-Mullerian hormone (AMH) levels respond to distinct ovarian stimulation methods in assisted reproductive technology (ART): Clues to better ART outcomes.

PURPOSE: We asked whether the relationship between anti-Mullerian hormone (AMH) value and the response to ovarian stimulation (OS) might be AMH value-related and differ for each regimen, aiming at getting clues as to how to choose OS protocols according to AMH levels. We further addressed how AMH value connects with ART outcome. METHODS: A total of 1112 women undergoing egg retrieval in ART were included. We adopted four OS protocols, that is, clomiphene, clomiphene + low-dose gonadotropins (Gns), GnRH (Gn-releasing hormone) + Gns (short), and GnRH antagonist. RESULTS: Anti-Mullerian hormone showed a stronger correlation with egg number compared with age over a wide age range. When patients were stratified into four groups by AMH value (<1, 1-2, 2-3, and 3≦ ng/mL), the relationship between AMH and egg number differed among differential OS regimes. The number of eggs rose as AMH and total doses of Gn increased. When analyzed for each AMH group, egg number, but not AMH, was associated with pregnancy rate. CONCLUSION: Different AMH levels exhibit characteristic responses to distinct OS regimens. To improve ART outcomes, personalized OS should be selected so as to maximize egg number, which seems to be a more precise variable than AMH for predicting pregnancy.

Identifying a possible factor for the increased newborn size in singleton pregnancies after assisted reproductive technology using cryopreserved embryos, in comparison with fresh embryos.

PURPOSE: To determine whether the cycle regimens that are used for endometrial preparation are associated with the birthweight (BW) after assisted reproductive technology (ART) using frozen-thawed embryo transfer (FET). METHODS: The BW of singletons who were born by ART using FET was compared retrospectively, according to whether a FET was conducted in a hormone replacement therapy cycle (HRT, n = 403) or an ovulatory cycle (OVL, n = 117). The BW after timed intercourse (NAT, n = 162) also was investigated. RESULTS: There were no significant differences in the age of the mothers, percentage of primiparas, gestational periods, Body Mass Index, and sex ratio between the HRT and OVL cycles. The average BW from HRT was significantly greater than that of OVL. The BW from HRT was also greater, compared with NAT, while statistical significance was not achieved between OVL and NAT. The putative factors affecting the BW, such as ovarian stimulation protocols, endometrial thickness, and the stage and quality of embryos, could not explain the difference in the BW between the HRT and OVL cycles. CONCLUSION: An increased BW from ART using FET seems to be ascribable to conditions of the endometrium, but not cryopreservation procedures per se, which might provide a mechanistic framework for understanding heavier neonates who are born by FET.

ASK1 and ASK2 differentially regulate the counteracting roles of apoptosis and inflammation in tumorigenesis.

Apoptosis and inflammation generally exert opposite effects on tumorigenesis: apoptosis serves as a barrier to tumour initiation, whereas inflammation promotes tumorigenesis. Although both events are induced by various common stressors, relatively little is known about the stress-induced signalling pathways regulating these events in tumorigenesis. Here, we show that stress-activated MAP3Ks, ASK1 and ASK2, which are involved in cellular responses to various stressors such as reactive oxygen species, differentially regulate the initiation and promotion of tumorigenesis. ASK2 in cooperation with ASK1 functioned as a tumour suppressor by exerting proapoptotic activity in epithelial cells, which was consistent with the reduction in ASK2 expression in human cancer cells and tissues. In contrast, ASK1-dependent cytokine production in inflammatory cells promoted tumorigenesis. Our findings suggest that ASK1 and ASK2 are critically involved in tumorigenesis by differentially regulating apoptosis and inflammation.

Characterization of transplacental transfer of paroxetine in perfused human placenta: development of a pharmacokinetic model to evaluate tapered dosing.

The aim of this study was to determine whether a tapered dosage regimen of paroxetine in pregnant women might be useful to avoid withdrawal syndromes in neonates after delivery. We characterized the transplacental transfer of paroxetine in perfused human placenta, fitting a pharmacokinetic model to the results and applying the model and parameters to evaluate a tapered dosage regimen. Paroxetine was perfused from the maternal or fetal side of an isolated human placental preparation with various perfusion protocols, and paroxetine concentrations in the effluent and placental tissue were determined. The transplacental pharmacokinetic parameters of paroxetine were estimated by simultaneous fitting of a five-compartment transplacental pharmacokinetic model to the set of paroxetine concentration profiles. The developed model and parameters were used to simulate the maternal and fetal concentrations of paroxetine, and the results were compared with reported data. Paroxetine showed a larger distribution volume in placental tissue and a smaller transplacental transfer as compared with antipyrine, a passive diffusion marker. A five-compartment model could well describe the transplacental transfer of paroxetine and could well simulate the maternal and umbilical venous concentrations of paroxetine at delivery. Transplacental transfer kinetic parameters of paroxetine were estimated by fitting a pharmacokinetic model to perfusion study data. The model and parameters appeared to be suitable for simulation of paroxetine kinetics in fetus. The model was also applicable to design a dosage regimen to avoid an abrupt decrease of paroxetine concentration in fetal plasma.

Increased risk of placenta previa is associated with endometriosis and tubal factor infertility in assisted reproductive technology pregnancy.

Although assisted reproductive technology (ART) is suspected to increase the risk of placenta previa, a life-threatening complication of pregnancy, the reason is poorly understood. We recruited consecutive 318 pregnancies conceived by ART in our clinic and examined relation of ten variables, i.e. maternal age, gravidity, parity, male or female fetus, previous abortion, previous cesarean delivery, endometriosis, ovulatory disorder, tubal disease, and male infertility, to placenta previa, by logistic regression analysis. As a result, we found that endometriosis (odds ratio = 15.1; 95% CI = 7.6-500.0) and tubal disease (odds ratio = 4.4; 95% CI = 1.1-26.3) were significantly associated with placenta previa. It would be preferable to take the increased risk of placenta previa into account in treating ART pregnancy with endometriosis and tubal disease.

Management of patient with arrhythmogenic right ventricular cardiomyopathy during pregnancy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiac disease that affects the right side of the heart and causes ventricular arrhythmias. It is considered as the most common cause of sudden cardiac death in young adults. However, risk and optimal management of ARVC during pregnancy and delivery remain unclear due to the small number of reported cases. Here we report a case of successful management of pregnancy and delivery in a patient with ARVC, who had a history of sustained ventricular tachycardia from her previous pregnancy.

Müllerian cyst of the uterus treated with laparoscopy and diagnosed using immunohistology.

Among uterine cystic tumors, uterine cyst arising from secondary Müllerian epithelium is exceedingly rare. A 45-year-old woman presented with pelvic cystic mass, which was initially diagnosed as a paraovarian cyst by ultrasound and magnetic resonance imaging. At laparoscopy, the cyst proved to be a pedunculated uterine cyst, which was easily resected. Histologically, the cyst wall was lined by fallopian epithelium and positively stained for WT-1, estrogen receptor, and progesterone receptor. The final diagnosis was Müllerian cyst of the uterus. Preoperative diagnosis of uterine Müllerian cyst is usually impossible. Laparoscopy is useful as a minimally invasive treatment to diagnose and resect the cyst at the same time. Specific immunostaining is useful to make a definite diagnosis of Müllerian cyst of the uterus.

Spontaneous cessation and recurrence of massive uterine bleeding can occur in uterine artery pseudoaneurysm after laparoscopically assisted myomectomy.

A uterine artery pseudoaneurysm (UAP) is a rare but life-threatening complication that can occur after gynecologic surgery. Herein, we present a case of a 38-year-old woman who presented with massive uterine bleeding one month after a laparoscopically assisted myomectomy. Although the bleeding ceased spontaneously, a massive hemorrhage reoccurred three weeks thereafter, and a ruptured perfusion sac at the right uterine artery was identified by computed tomography angiography and ultrasonography. The patient was treated with transfemoral catheter embolization of the right uterine artery, and complete resolution of the UAP was successfully obtained. Our case suggests that a UAP may be a cause of unexplained repetitive metrorrhagia after myomectomy.

Retreatment with nedaplatin in patients with recurrent gynecological cancer after the development of hypersensitivity reaction to carboplatin.

AIM: Platinum is a milestone drug against gynecologic malignancies. The purpose of this retrospective study was to investigate the feasibility of replacing carboplatin with nedaplatin in patients who had developed a hypersensitivity reaction to carboplatin. MATERIAL AND METHODS: Fifteen patients with recurrent gynecologic cancer (12 ovarian, 1 fallopian tube, 1 endometrial and 1 cervical cancer) who had experienced a hypersensitivity reaction to carboplatin and a possible clinical indication for continuing treatment with platinum were treated with nedaplatin (80 mg/m(2) )-containing regimen. RESULTS: The total number of nedaplatin cycles given was 137 (range 1-29). Four (27%) patients developed hypersensitivity reactions on the second, second, fourth, and ninth administration, respectively. The severities of all the hypersensitivity reactions were grade 3 or less. The other 11 patients (73%) had no nedaplatin-associated hypersensitivity reactions. The incidence of hypersensitivity reactions in the paclitaxel and nedaplatin group (three of four, 75%) was more frequent than the docetaxel and nedaplatin group (none of seven, P=0.024). The objective response rate in eleven patients with measurable disease was 36% (complete response at 9% and partial response at 27%), and the disease control rate was 73% (stable disease at 36%). CONCLUSION: Nedaplatin-associated hypersensitivity reactions are not rare in patients who developed allergic reactions to carboplatin. Retreatment of carboplatin-allergic patients with nedaplatin cannot be recommended without careful consideration of the potential risks and benefits.

Regulation of SIRT1 determines initial step of endometrial receptivity by controlling E-cadherin expression.

Sirtuin 1 (SIRT1), originally found as a class III histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. We examined the role of SIRT1 in the regulation of uterine receptivity using Ishikawa and RL95-2 endometrial carcinoma cell lines. Exogenous expression of SIRT1 significantly enhanced E-cadherin expression, while small interfering RNA-mediated depletion of endogenous SIRT1 resulted in a significant reduction of E-cadherin expression. A SIRT1 activator resveratrol elevated E-cadherin expression in a dose dependent manner, while SIRT1 repressors nicotinamide and sirtinol exhibited a dose dependent reduction of E-cadherin expression. We also showed that both forced expression of SIRT1 and activation of SIRT1 promote E-cadherin-driven reporter gene constructs, and SIRT1 is localized at E-cadherin promoter containing E-box elements in Ishikawa cells. Using an in vitro model of embryo implantation, we demonstrate that exogenous expression of SIRT1 and stimulation of SIRT1 activity resulted in the Ishikawa cell line becoming receptive to JAR cell spheroid attachment. Furthermore, resveratrol enhanced E-cadherin and Glycodelin protein expression at sites of intercellular contact, suggesting an additive role of resveratrol in promoting implantation. The initial step of human reproduction depends on the capacity of an embryo to attach and implant into the endometrial wall, and these results revealed the novel mechanism that activation and increased expression of SIRT1 play an important role in uterine receptivity.

Interleukin-1ß stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis.

STUDY QUESTION: Is thymic stromal lymphopoietin (TSLP) involved in the pathophysiology of endometriosis? SUMMARY ANSWER: TSLP is up-regulated by interleukin (IL)-1ß and may be involved in the development of endometriosis. WHAT IS KNOWN ALREADY: Endometriosis is a chronic inflammatory disease in which the Th2 immune response is activated and has been suggested to promote the disease. TSLP is a master cytokine that drive Th2 immune response. STUDY DESIGN, SIZE, DURATION: A laboratory study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary cultures of endometrioma stromal cells (ESCs) were treated with IL-1ß, a typical inflammatory cytokine associated with endometriosis. Gene expression of TSLP in ESCs and secretion of TSLP protein from ESCs were studied using quantitative PCR and a specific ELISA. Interferon γ (IFNγ), a typical Th1 cytokine, and IL-4, a typical Th2 cytokine, were added to the culture to evaluate their effect on the IL-1ß-induced secretion of TSLP. Inhibitors of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK and stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) were added to the culture to examine intracellular signals involved in IL-1ß-induced TSLP secretion. The expression of TSLP in endometrioma tissue was examined by immunohistochemistry. The concentration of TSLP in the serum and peritoneal fluid (PF) of women with or without endometriosis was measured with a specific ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: IL-1ß stimulated the expression of TSLP mRNA and secretion of TSLP protein from ESCs. IL-4 enhanced the IL-1ß-induced TSLP secretion from ESCs, while IFNγ reduced it. Inhibitors of p42/44 MAPK, p38 MAPK and SAPK/JNK suppressed the IL-1ß-induced secretion of TSLP from ESCs. Positive immunostaining of TSLP was observed in the stroma of endometrioma tissue. TSLP concentrations in the serum and PF were both higher in women with endometriosis compared with those without endometriosis. LIMITATIONS, REASONS FOR CAUTION: The present study was only in vitro. The samples used for culture were endometrioma tissues, not including other types of endometriosis. Therefore, the present findings should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: This study provided new insights in the Th2 immune response-related mechanism in endometriosis. STUDY FUNDING: This study is partly supported by grants from the Ministry of Health, Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. The authors have no conflicts of interest to declare.

Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary.

BACKGROUND: Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins) have been identified as targets of resveratrol. Sirtuin 1 (SIRT1), originally found as an NAD+-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary. METHODS: The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining. RESULTS: SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol. CONCLUSIONS: These results suggest a novel mechanism that resveratrol could enhance progesterone secretion and expression of luteinization-related genes in the ovary, and thus provide important implications to understand the mechanism of luteal phase deficiency.

Prediction and evaluation of fetal toxicity induced by NSAIDs using transplacental kinetic parameters obtained from human placental perfusion studies.

AIM: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in full-term pregnant women leads to fetal or neonatal toxicity, such as constriction of the ductus arteriosus (DA) and persistent pulmonary hypertension in the newborn. The aim of this study was to predict quantitatively the fetal toxicity of three NSAIDs (antipyrine, salicylic acid and diclofenac) using the transplacental pharmacokinetic parameters obtained from our previous placental perfusion studies. METHODS: Human fetal plasma concentration profile after oral administration of each NSAID to the mother was estimated using the transplacental pharmacokinetic parameters and pharmacokinetic parameters in adult women. The fetal plasma concentration-response relationship for the three NSAIDs was estimated by pharmacokinetic/pharmacodynamic analysis of the results of previous studies investigating the effects of NSAIDs on the ratio of inner diameter of the DA to that of the pulmonary artery (DA/PA) in rats and the plasma concentration profiles of NSAIDs in pregnant rats. RESULTS: The risk of constriction of the DA was well predicted by the model. Mean DA/PA ratio after oral administration of diclofenac to the mother was estimated to be 39.0%, whereas both of the corresponding values after oral administration of antipyrine and salicylic acid were estimated to be 5.9%. These results suggest that the fetal risk of diclofenac is higher than those of salicylic acid and antipyrine. CONCLUSIONS: This study presents a novel approach to predict quantitatively the fetal risk of NSAIDs administered to the mother. Human placental perfusion study and pharmacokinetic/pharmacodynamic analysis may provide basic data for predicting human fetal toxicity of drugs.

Genome-wide single nucleotide polymorphism arrays as a diagnostic tool in patients with synchronous endometrial and ovarian cancer.

OBJECTIVE: Synchronous carcinomas in the endometrium and ovaries can be a single primary tumor with metastasis (SPM) or dual primary tumors (DP). Although the prognosis of DP without any metastases is significantly better than that of SPM, pathological diagnosis is difficult in tumors with similar histological features. MATERIALS AND METHODS: In 10 tumors from 5 patients with synchronous endometrial and ovarian carcinomas, 250K single nucleotide polymorphism arrays were performed. The patients were genetically diagnosed according to the pattern of copy number alterations (CNAs), in addition to microsatellite status and mutational analysis of PIK3CA, PTEN, K-Ras, and CTNNB1. RESULTS: Of the 5 patients, 3 exhibited identical CNA patterns, including type, loci, and degree of each alteration in the endometrial and ovarian carcinomas. The other 2 exhibited CNAs only in either endometrial or ovarian carcinoma. All 5 tumors had 1 or more genetic mutations in the genes examined. One patient exhibited mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other 4 exhibited concordant mutations. Overall, 4 of the 5 patients were genetically diagnosed with SPM, and the remaining 1 with DP. The pathological diagnosis was not in agreement with the genetic diagnosis in 4 of the 5 patients. CONCLUSIONS: Genome-wide genotyping diagnosis may represent a useful approach for distinguishing between SPM and DP in synchronous endometrial and ovarian carcinomas.

Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss.

We describe successful ovulation induction with low-dose hCG administration in addition to hMG in a patient with refractory hypothalamic amenorrhea. A 24-year-old woman with weight loss-related amenorrhea underwent ovulation induction and intracytoplasmic sperm injection (ICSI). Administration of exogenous gonadotropins was ineffective in ovulation induction. Supplementation with low-dose hCG in order to increase luteinizing hormone (LH) activity in the late follicular phase produced late folliculogenesis and steroidogenesis, and ovulation was then successfully induced. This report reacknowledges the critical role that LH plays cooperatively with follicle-stimulating hormone in both folliculogenesis and steroidogenesis.

Uterine arteriovenous fistula treated with repetitive transcatheter embolization: case report.

Uterine arteriovenous fistula (AVF) is a rare entity, but may lead to life-threatening hemorrhage. Although transcatheter embolization, surgical ligation, or hysterectomy would be considered for treatment of uterine AVF, there is poor knowledge as to how gynecologists can manage the uterine AVF with multiple large inflow arteries. Herein we report a uterine AVF successfully treated using multiple-step transcatheter embolization. The patient, a 58-year-old postmenopausal woman with a history of dilation and curettage, had intermittent massive uterine bleeding. Radiologic imaging revealed the presence of a large vasculature mass. The mass occupied the entire pelvis, and the source of hemorrhage was identified as an accompanying AVF. We thought that surgical intervention was contraindicated because of the potential risk of uncontrollable intraoperative bleeding. Multiple-step transcatheter embolization was performed, with complete resolution of the AVF. Thereafter, the patient had no further uterine bleeding. Multiple-step transcatheter embolization might be the most beneficial and efficient treatment option for a uterine AVF with multiple large inflow arteries.

The decision-making process for the fate of frozen embryos by Japanese infertile women: a qualitative study.

BACKGROUND: Previous studies have found that the decision-making process for stored unused frozen embryos involves much emotional burden influenced by socio-cultural factors. This study aims to ascertain how Japanese patients make a decision on the fate of their frozen embryos: whether to continue storage discard or donate to research. METHODS: Ten Japanese women who continued storage, 5 who discarded and 16 who donated to research were recruited from our infertility clinic. Tape-recorded interviews were transcribed and analyzed for emergent themes. RESULTS: A model of patients' decision-making processes for the fate of frozen embryos was developed, with a common emergent theme, "coming to terms with infertility" resulting in either acceptance or postponing acceptance of their infertility. The model consisted of 5 steps: 1) the embryo-transfer moratorium was sustained, 2) the "Mottainai"- embryo and having another child were considered; 3) cost reasonability was taken into account; 4) partner's opinion was confirmed to finally decide whether to continue or discontinue storage. Those discontinuing, then contemplated 5): the effect of donation. Great emotional conflict was expressed in the theme, steps 2, 4, and 5. CONCLUSIONS: Patients' 5 step decision-making process for the fate of frozen embryos was profoundly affected by various Japanese cultural values and moral standards. At the end of their decision, patients used culturally inherent values and standards to come to terms with their infertility. While there is much philosophical discussion on the moral status of the embryo worldwide, this study, with actual views of patients who own them, will make a significant contribution to empirical ethics from the practical viewpoint.

Alternative strategies to in vitro fertilization/intracytoplasmic sperm injection treatment for aged infertile women.

PURPOSE: This study aimed to maximize the chance of pregnancy and provide an optimal protocol for infertile female patients of advanced reproductive age as an alternative to in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. METHODS: We retrospectively analyzed medical records of 432 infertile women aged ≥38 at the beginning of the treatment. Stepwise non-IVF/ICSI treatments using timed intercourse or intrauterine insemination, with or without controlled ovarian stimulation, were adopted for all patients. In this population, we extracted 8 representative infertility factors and examined these effects on fertility rate by calculating clinical pregnancy rate. RESULTS: The prognosis for infertile women possessing at least one of the three factors, 'advanced female age (≥42 years)', 'endometriosis/adenomyosis', and 'tubal infertility' was apparently poor because only 5 out of 155 women were able to conceive (1.02% per cycle). In contrast, 95 patients without the four factors, 'advanced female age', 'endometriosis/adenomyosis', 'tubal infertility', and 'male infertility', were more likely to conceive (9.14% per cycle). CONCLUSIONS: Fertility centers can offer appropriate protocols for non-IVF/ICSI treatment and establish guidelines for aged infertile patients by examining infertility factors and considering their combinations.