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.

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.

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.

Comparison of Pregnancy Outcomes Between Fresh Embryo Transfer in a Natural IVF Cycle and IUI Cycle Among Infertile Young Women.

Background: The purpose of the current study was comparing pregnancy outcomes for natural cycle in vitro fertilization (IVF) per fresh embryo transfer (ET) and oocyte pick-up (OPU) in intrauterine insemination (IUI). Methods: This was a retrospective cohort study of women who underwent either IUI (n=246) or OPU with fresh ET for natural cycle IVF (n=291), conducted between April 2017 and February 2018 at the Center for Reproductive Medicine and Implantation Research, Sugiyama Clinic Shinjuku, Tokyo, Japan. Patients in both groups did not receive ovarian stimulation and luteal support; gonadotropin-releasing agonist spray was administered 35 hr before OPU or IUI. The clinical pregnancy rate was compared between the IUI and IVF groups. Data analysis was based on the number of cycles. The p≦0.05 was considered significant. Results: The clinical pregnancy rate per OPU in the IVF group was higher than the one in IUI group (20.6% vs. 10.1%), and the difference was significant (p<0.01). The pregnancy rate for natural cycle IVF calculated per fresh ET was 36.8%. The miscarriage rate did not significantly differ between the IVF (4.1%) and IUI (8.0%) groups. Conclusion: Fresh ET in natural cycle IVF provides a higher implantation rate than IUI.

Prevalence of and risk factors for chronic endometritis in patients with intrauterine disorders after hysteroscopic surgery.

OBJECTIVE: To identify the prevalence of and risk factors for chronic endometritis (CE) in patients with intrauterine disorders and the therapeutic efficacy of hysteroscopic surgery in the treatment of CE without antibiotic therapy. DESIGN: Prospective cohort study. SETTING: Hospital specializing in reproductive medicine. PATIENT(S): The study population consisted of 350 women with infertility, of whom 337 were recruited, who underwent hysteroscopic surgery between November 2018 and June 2021. Eighty-nine consecutive patients without intrauterine disorders were also recruited as controls. INTERVENTION(S): Endometrial samples were collected during the surgery for CD138 immunostaining for the diagnosis of CE. In women diagnosed with CE, endometrial biopsy was performed without antibiotic use in the subsequent menstrual cycle. MAIN OUTCOME MEASURE(S): Prevalence of and risk factors for CE in intrauterine disorders and therapeutic effects of hysteroscopic surgery on CE. RESULT(S): The prevalence of CE with ≥5 CD138-positive cells in women with no intrauterine disorder and with endometrial polyps, myomas, intrauterine adhesions (IUAs), and septate uterus was 15.7%, 85.7%, 69.0%, 78.9%, and 46.2%, respectively. A multivariate analysis revealed that CE was diagnosed significantly more often in the endometrial polyp (odds ratio, 27.69; 95% confidence interval, 15.01-51.08) and IUA groups (odds ratio, 8.85; 95% confidence interval, 3.26-24.05). The rate of recovery from CE with surgery in women with endometrial polyps, myomas, IUA, and septate uterus was 89.7%, 100%, 92.8%, and 83.3%, respectively. CONCLUSION(S): Endometrial polyp and IUA were risk factors for CE. Most CE cases with intrauterine disorders were cured with hysteroscopic surgery without antibiotic therapy, regardless of the type of intrauterine abnormalities.

Analysis of the therapeutic effects of hysteroscopic polypectomy with and without doxycycline treatment on chronic endometritis with endometrial polyps.

PROBLEM: We aimed to compare the therapeutic effects of hysteroscopic polypectomy with and without doxycycline treatment on chronic endometritis (CE) with endometrial polyps. METHOD OF STUDY: DESIGN: A cross-sectional study was conducted on 267 infertile patients, of whom 243 were recruited, who underwent hysteroscopic polypectomy between March 2019 and March 2020. During surgery, the endometrial specimens for the immunohistochemistry analysis of the plasma cell marker CD138 and for the intrauterine bacterial culture were obtained to diagnose CE, and the prevalence of CE was analyzed. Of the 222 women who were diagnosed with CE after polypectomy, we treated 62 women with doxycycline (antibiotic group) and did not provide antibiotics in 160 women (non-antibiotic group). RESULTS: Most of the infertile patients with endometrial polyps had CE (92.6%). The recovery rate from CE by hysteroscopic polypectomy was significantly higher in the non-antibiotic group than in the antibiotic group (88.8% and 58.1%, respectively, p < 0.0001). The duration of recovery from CE in the non-antibiotic group was shorter than that in the antibiotic group (42.6 ± 41.0 and 56.5 ± 32.3 days, respectively, p < 0.0001). The clinical pregnancy rate within 6 months in non-antibiotic group was higher than that in the antibiotic group (63.2% and 43.8%, respectively, p = 0.034). CONCLUSION: Endometrial polyps are significantly associated with CE. Most CE patients with endometrial polyps had been cured by polypectomy without doxycycline. Inappropriate antibiotic therapy may delay recovery from CE and decrease the efficacy of polypectomy on CE and pregnancy rates.

Effects of Periconceptional Multivitamin Supplementation on Folate and Homocysteine Levels Depending on Genetic Variants of Methyltetrahydrofolate Reductase in Infertile Japanese Women.

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.1%), 100 (48.8%) and 33 (16.1%) had MTHFR CC, CT and TT, respectively. Serum folate and homocysteine levels in women with homozygous mutant TT were significantly lower and higher, respectively, than those in women with CC and CT. In 54 women (26.3% of all women) with a risk of NTDs, multivitamin supplementation containing folic acid and vitamin D for one month increased folate level (5.8 ± 0.9 to 19.2 ± 4.0 ng/mL, p < 0.0001) and decreased the homocysteine level (8.2 ± 3.1 to 5.8 ± 0.8 nmol/mL, p < 0.0001) to minimize the risk of NTDs in all women, regardless of MTHFR genotype. Regardless of MTHFR genotype, multivitamin supplements could control folate and homocysteine levels. Tests for folate and homocysteine levels and optimal multivitamin supplementation in women with risk of NTDs one month or more before pregnancy should be recommended to women who are planning a pregnancy.

Increasing number of implantation failures and pregnancy losses associated with elevated Th1/Th2 cell ratio.

PROBLEM: We aimed to assess whether an imbalance of T-helper (Th) 1 and Th2 cells contributes to implantation failure and pregnancy loss. METHOD OF STUDY: In this cross-sectional study, 197 consecutive patients with a history of repeated implantation failure (RIF) after three or more embryo transfer (ET) cycles and/or recurrent pregnancy loss (RPL) after two or more clinical pregnancy losses underwent Th cell testing. After excluding 42 women aged ≥44 and 9 with vitamin D supplementation, we recruited 146 women including 79 with RIF and 81 with RPL. Fourteen women had a history of both RIF and RPL. We also recruited 45 fertile women and 40 general infertile women without a history of in vitro fertilization treatment. This study was approved by the local ethics committee. RESULTS: There was no significant difference in IFN-γ-producing Th1 and IL-4-producing Th2 cell levels between the fertile and general infertile women, but Th1 cell levels and the Th1/Th2 cell ratio were significantly higher in the women with ≥4 ET cycles and ≥2 pregnancy losses than in the fertile and general infertile women. In the general infertile women, the total livebirth rates including natural conception after two ET cycles in the normal and high Th1/Th2 groups (Th1/Th2 <11.8 and ≥11.8, respectively) were 66.7% and 87.5%, respectively (p = .395). CONCLUSIONS: A high Th1/Th2 cell ratio was linked to ≥4 implantation failure cycles and ≥2 pregnancy losses but not to general infertility.

Impact of chronic endometritis on endometrial receptivity analysis results and pregnancy outcomes.

BACKGROUND: The aim of this study is to evaluate the relationship between chronic endometritis (CE) and a personalized window of implantation (WOI), identified by results of endometrial receptivity analysis (ERA), and pregnancy outcomes following embryo transfer (ET) based on the ERA outcomes. METHODS: The single-center, cross-sectional study was designed. The study population consisted of 101 infertile women who underwent endometrial sampling between June 2018 and February 2020. We recruited 88 patients who underwent ERA testing and immunohistochemistry of the plasma cell marker CD138 to diagnose CE within 3 months of testing. Subjects were divided into three groups as follows: 33 without CE (non-CE group); 19 with untreated CE at ERA testing (CE group); and 36 successfully treated for CE before ERA testing (cured-CE group). CE diagnosis was defined as ≥5 CD138-positive plasma cells per 10 random stromal areas at ×400 magnification. RESULTS: In non-CE, CE, and cured-CE groups, the numbers of CD138-positive cells were 0.7 ± 1.0, 28.5 ± 30.4, and 1.3 ± 1.3, respectively (p < .001). The rates of "receptive" endometrium in non-CE and cured-CE groups were 57.6% (19 women) and 50.0% (18 women), respectively; however, in the CE group, this rate was significantly lower than the other two groups (p = .009) at only 15.8% (3 women). After CE were treated prior or posterior to the ERA test in cured-CE or CE groups, the clinical pregnancy rates at the first ET in non-CE, CE, and cured-CE groups were 77.8% (21/27 cycles), 22.2% (4/18 cycles), and 51.7% (15/29 cycles), respectively (p < 0.001). CONCLUSION: CE had detrimental effects on the individual WOI, leading to embryo-endometrial asynchrony; therefore, diagnosis and treatment of CE should be done before ERA testing.

Influence of Negative Emotional Expressions on the Outcomes of Shared Decision Making During Oncofertility Consultations in Japan.

This report examines how negative emotional expressions (NEE) influence the consequences of shared decision making (SDM) in oncofertility treatment among 32 young female cancer patients and 19 family members. Using a cross-sectional observational study, results showed that NEE influence the outcome consequences of SDM related to patients' decisions about desired treatment(s) and that the absence of negative emotional reactions to information from doctors was related to willingness to receive the desired treatment. This suggests that healthcare providers need to be sensitive to NEE of patients and their families, and highlights the need for psychological counseling before oncofertility consultation.

Relationship between Semenogelins bound to human sperm and other semen parameters and pregnancy outcomes.

BACKGROUND: Semenogelins (SEMGs) are major components of human seminal vesicle secretions. Due to SEMG's sperm-motility inhibitor, a significant negative correlation between sperm motility and the proportion of SEMG-bound spermatozoa (SEMG+) was found in asthenozoospermic patients. SEMGs also show intrinsic inhibitory capability for sperm capacitation; however, studies on actual clinical specimens have not been conducted. METHODS: To reveal the relationship between SEMGs and the fertilizing capacity of sperm from male infertile patients who are not restricted to asthenozoospermia, we measured the proportion of SEMG+ in the spermatozoa of 142 male infertile patients. The pregnancy outcomes in partners of these patients were retrospectively analyzed using questionnaires. RESULTS: Among examined semen parameters, only the total SEMG-unbound sperm count showed a tendency to be different between the spontaneous pregnancy or intra-uterine-insemination-pregnancy groups and in-vitro-fertilization- or intracytoplasmic-sperm-injection-pregnancy groups. It was elevated in the former group, which includes patients who used in vivo fertilization. CONCLUSIONS: The total SEMG-unbound sperm count would be a relevant parameter for in vivo fertilization. This result suggests that SEMGs inhibit ectopic capacitation before sperm reach the fertilization site and that the number of total SEMG-unbound sperm is a parameter directly linked to the possibility of in vivo fertilization.

CONTEXTE: Les séménogélines (SEMG) sont des composantes principales des sécrétions des vésicules séminales humaines. En raison de la présence sur SEMG d'un inhibiteur de la mobilité des spermatozoïdes, une corrélation significative a été rapportée entre la mobilité des spermatozoïdes et le pourcentage de spermatozoïdes liés à SEMG chez des patients asthénozoospermiques. Les SEMG possèdent aussi une capacité intrinsèque d'inhibition de la capacitation; aucune étude n'a cependant été réalisée sur des échantillons de sperme utilisés en pratique clinique quotidienne. MATÉRIEL ET MÉTHODES: De façon à mettre en évidence une relation entre les SEMG et la capacité fécondante de spermatozoïdes d'hommes inféconds qui ne soient pas seulement des patients asthénozoospermiques, nous avons mesuré la proportion de spermatozoïdes SEMG+ (liés à SEMG) chez 142 patients inféconds. L'issue des grossesses chez les partenaires de ces patients a été rétrospectivement analysée à partir de questionnaires. RÉSULTATS: Parmi les paramètres spermatiques analysés, seul le nombre total de spermatozoïdes non liées à SEMG montre une tendance à être différent entre le groupe de grossesses obtenues spontanément ou par insémination intra-utérine et le groupe de grossesses obtenues par fécondation in vitro ou injection intra-cytoplasmique d'un spermatozoïde. Ce nombre total était élevé dans le premier groupe qui incluait des patients utilisant une fécondation in vivo. CONCLUSIONS: Le nombre total de spermatozoïdes non liés à SEMG pourrait être un paramètre pertinent pour la fécondation in vivo. Ces résultats suggèrent que les SEMG inhibent la capacitation ectopique avant que les spermatozoïdes n'atteignent le site de fécondation, et que le nombre total de spermatozoïdes non liés à SEMG est. un paramètre directement lié à la possibilité de fécondation in vivo. MOTS-CLÉS: Protéine plasmatique séminale, Infécondité masculine, Séménogélines, IIU, FIV, ICSI, Issues de grossesses.

Effects of in vivo exposure to eggs with sperm-immobilizing antibodies in follicular fluid on subsequent fertilization and embryo development in vitro.

Aims: It has been shown that supplementation of patients' sera that contains sperm-immobilizing antibodies results in failure of fertilization and embryo development in vitro. The present study was carried out to investigate if exposing retrieved eggs to a high number of sperm-immobilizing antibodies in the follicular fluid (FF) in vivo affected subsequent fertilization and embryo development in vitro, even if they were washed with an antibody-free culture medium. Methods: Patients' sera and their FF were collected in 15 in vitro fertilization-embryo transfer (IVF-ET) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) treatment cycles from 11 infertile women with sperm-immobilizing antibodies in their sera. Quantitative sperm-immobilizing antibody titers (SI50 titers) in the sera and FF were evaluated. The fertilization rate, good-quality embryo rate and implantation rate by IVF-ET were compared between infertile patients having higher (10≤) SI50 titers and lower (<10) SI50 titers in their FF. Results: There was a significant correlation in the SI50 titers between the patients' sera and their FF (P < 0.0001). After thoroughly washing the collected eggs in culture medium without the patient's serum before IVF, there was no difference in the fertilization rate in the patients with high (10≤) and low (<10) SI50 titers in their FF (P = 0.62). However, the good-quality embryo rate in the patients with a high SI50 titer was significantly lower than patients with a low antibody titer (P < 0.05). There was no significant difference in the implantation rate between the two groups (P = 0.33). Conclusions: Similar amounts of sperm-immobilizing antibodies existed in the patients' FF and in their sera. ICSI did not seem to be necessary in patients having the antibodies if their sera were not supplemented in the culture media. Even with careful manipulation of eggs, it might be suggested that the harmful effects of sperm-immobilizing antibodies on embryo development cannot be completely avoided, especially in patients with high SI50 titers in the FF. (Reprod Med Biol 2006; 5: 137-143).

Severe ovarian hyperstimulation syndrome in a 42-year-old woman with successful pregnancy after intracytoplasmic sperm injection embryo transfer.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovulation induction for infertile women. It has been shown that patients suffering from OHSS are generally young because OHSS depends on the patient's ovarian reserve. Therefore, women ≥40 years of age seldom suffer from the severe form of OHSS. In the present study, we report a case of severe OHSS that occurred in a 42-year-old woman with a successful pregnancy after intracytoplasmic sperm injection (ICSI)-embryo transfer. She had been diagnosed as having polycystic ovary syndrome (PCOS). After 5 cycles of unsuccessful treatment with gonadotropins plus intrauterine insemination for her husband's asthenozoospermia, the treatment with assisted reproductive technology (ART) was indicated. In the third ART attempt, the patient was treated by ICSI-embryo transfer (ET) and she developed severe OHSS at 4 weeks' gestation. On admission, marked hemoconcentration, oligouria and hypo-albuminemia were diagnosed. A continuous autotransfusion system of ascites, which was developed to expand circulating plasma volume without exogenous albumin, was carried out for 5 h at a rate of 100-200 mL/h once a day for a total of 5 days. The course of the pregnancy was uneventful. At 37 weeks' gestation, a healthy baby boy weighing 3336 g was born by cesarean section when the patient was 43 years of age. The postoperative course was also uneventful. To the best of our knowledge, the present report describes the oldest woman showing severe OHSS. (Reprod Med Biol 2005; 4: 265-269).

Serum leptin concentrations in patients with severe ovarian hyperstimulation syndrome during in vitro fertilization-embryo transfer treatment.

OBJECTIVE: To investigate the changes in serum leptin concentration in the conception cycle of severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Prospective longitudinal study of 66 IVF-ET cycles between May 2000 and June 2002. SETTING: Infertility outpatient clinic at a Japanese medical school. PATIENT(S): Infertile patients undergoing IVF-ET cycles at the infertility outpatient clinic were divided into three groups consisting of group 1 (conception-cycle patients with severe OHSS, n = 9), and group 2 (conception cycle, non-OHSS, n = 28), and group 3 (nonconception cycle, non-OHSS, n = 29). INTERVENTION(S): Blood samples were collected at five different periods. Period I, on the first day of ovarian stimulation with FSH; period II, at hCG administration before oocyte retrieval; period III, 7 days after oocyte retrieval; period IV, 14 days after oocyte retrieval; and period V, 21 days after oocyte retrieval. MAIN OUTCOME MEASURE(S): Serum leptin concentration. RESULT(S): The serum leptin concentration was low in the OHSS group compared with that of the non-OHSS groups in all serum samples, with significant levels at periods III (vs. groups 2 and 3; P<.05) and IV (vs. group 3; P<.01). A twofold increase of leptin concentration from period I to period II (P<.05) was observed in all groups. CONCLUSION(S): The change pattern in serum leptin concentration might provide a great contribution to the pathophysiology development of OHSS patients during assisted reproductive treatment.

Usefulness and prognostic value of transvaginal hydrolaparoscopy in infertile women.

OBJECTIVE: To evaluate the usefulness and prognostic value of transvaginal hydrolaparoscopy (THL) in infertile women. DESIGN: Retrospective study. SETTING: Jichi Medical School Hospital, Tochigi, Japan. PATIENT(S): Thirty-six patients who were followed up for 6 months or longer after THL was performed. INTERVENTION(S): Transvaginal hydrolaparoscopy findings in comparison with hysterosalpingography (HSG). MAIN OUTCOME MEASURES: Transvaginal hydrolaparoscopy findings, HSG findings, treatment strategy, and prognosis. RESULT(S): Twenty of 36 patients (55.5%) became pregnant, including 7 by coitus, 7 by artificial insemination with the husband's semen, and 6 by assisted reproductive technology (ART). In 11 of these pregnant patients, information obtained during THL differed from findings on HSG. CONCLUSION(S): Transvaginal hydrolaparoscopy is useful in selecting a future treatment strategy.

Randomized study comparing day 2 versus day 3 elective transfer of two good-quality embryos.

Objective: The number of embryos transferred is very important to avoid multiple pregnancies without compromising pregnancy rates in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET). We established criteria for the elective transfer of two embryos (age <40, first treatment cycle, good-quality embryos ≥3) to avoid high-order multiple pregnancies, and reported their usefulness. In the current study, we compared the clinical outcome of day 2 versus day 3 elective transfer of two good-quality embryos, in order to investigate the day of preferential transfer. Methods: A total of 228 cycles were treated with IVF/ICSI-ET from August 1999 to August 2002. From this total, 114 patients who were less than 40 years old and also had a first treatment cycle were enrolled in the present study (50.0%). The elective transfer of two good-quality embryos was carried out in 36 cycles (31.6%). Patients were randomized for transfer on either day 2 or day 3 after oocyte retrieval. Results: The pregnancy rate of women who received two good-quality embryos was 44.4% (16 out of 36). The multiple pregnancy rate was 12.5% (two out of 16) and all pregnancies outcomes were twins. There were no significant differences between day 2 and day 3 ET for the following criteria: the number of cycles (24, 12); age (32.8 ± 3.4 years, 32.5 ± 2.7 years); number of oocytes retrieved (10.0 ± 3.3, 9.0 ± 6.0); number of embryos developed (7.6 ± 3.5, 6.9 ± 3.7); and number of good-quality embryos cryopreserved (3.5 ± 2.7, 3.6 ± 2.1). Higher pregnancy and implantation rates were obtained in day 3 ET than day 2 ET (37.5 and 20.8% in day 2 ET vs 58.3 and 33.3% in day 3 ET); however, there were no significant differences. Conclusion: Day 3 ET appears to be preferable to achieve more viable embryos than day 2 ET. (Reprod Med Biol 2004; 3: 99-104).

Successful pregnancy following conservative treatment of massive ascites associated with acute Chlamydia trachomatis peritonitis.

It is well known that Chlamydia trachomatis causes acute and chronic pelvic inflammatory disease including salpingitis. We describe a case of successful pregnancy following conservative treatment of massive ascites associated with acute Chlamydia trachomatis peritonitis. In this present case, we conservatively treated a woman with acute chlamydial salpingitis accompanied with marked ascites and an adnexal mass that simulated a malignant neoplasm. Elevated CA125 and CA19-9 also suggested a malignancy at the time of diagnosis, however following treatment they decreased to below the cut-off value, and were useful in identifying the efficacy of medical treatment. The patient subsequently became pregnant after infertility treatment and underwent a normal vaginal delivery. We conclude that the possibility of Chlamydia trachomatis peritonitis should be considered when a patient presents with ascites and an adnexal mass in sexually active women. (Reprod Med Biol 2004; 3: 217-221).