Association between endometriosis and perinatal complications: a case-control study.

BACKGROUND: Recently, a history of endometriosis has been reported to be associated with several perinatal complications. However, it is unknown whether pre-pregnancy treatment for endometriosis reduces perinatal complications. In this study, we aimed to clarify the association between endometriosis and perinatal complications and investigate whether there is a significant difference in the incidence of placenta previa depending on the degree of surgical completion of endometriosis before pregnancy. METHODS: This case-control study included 2781 deliveries at the Hirosaki University Hospital between January 2008 and December 2019. The deliveries were divided into a case group with a history of endometriosis (n = 133) and a control group without endometriosis (n = 2648). Perinatal outcomes and complications were compared between the case and control groups using a t-test and Fisher's exact test. Multiple logistic regression models were used to identify the risk factors for placenta previa. Additionally, we examined whether the degree of surgical completion of endometriosis before pregnancy was associated with the risk of placenta previa. RESULTS: Patients with a history of endometriosis had a significantly higher risk of placenta previa (crude odds ratio, 2.66; 95% confidence interval, 1.37‒4.83). Multiple logistic regression analysis showed that a history of endometriosis was a significant risk factor for placenta previa (adjusted odds ratio, 2.30; 95% confidence interval, 1.22‒4.32). In addition, among patients with revised American Society for Reproductive Medicine stage III-IV endometriosis, the incidence of placenta previa was significantly lower in patients who underwent complete surgery (3/51 patients, 5.9%) than in those who did not (3/9 patients, 33.3%) (p = 0.038). CONCLUSIONS: A history of endometriosis is an independent risk factor for placenta previa. Given the limitations of this study, further research is needed to determine the impact of endometriosis surgery on perinatal complications.

Sexual reproductive health and rights awareness among members of the Japan Society of Obstetrics and Gynecology.

AIM: The aim of this study was to determine the level of awareness of sexual reproductive health and rights (SRHR) among the members of the Japan Society of Obstetrics and Gynecology (JSOG) and identify what the JSOG should do to address SRHR issues. METHODS: A survey questionnaire on JSOG members' awareness of SRHR and what the JSOG should address regarding SRHR was administered in 2019 and 2023. Changes in awareness and the issues that should be addressed from the first to the second survey were evaluated. RESULTS: Seven hundred twelve members responded to the first survey and 506 to the second. Response rates were 4.2% and 2.9%, respectively. There was a significant increase in the number of respondents in the second survey who were aware of sexual reproductive health (SRH) and Sustainable Development Goals (SDGs) compared with the first survey (SRH: 72.6%-86.4%; SDGs: 33.8%-86.4%). Most respondents agreed that SRHR should be promoted. In the first survey, cervical cancer was the most important issue, followed by women's right to self-determination and family planning/contraception. In the second survey, women's right to self-determination was the most important issue. Several free responses highlighted the importance of comprehensive sexuality education as a significant concern for SRHR. CONCLUSION: Between 2019 and 2023, the level of awareness of SRHR among JSOG members increased. The identification of SRHR issues that should be addressed by the JSOG was confirmed. The JSOG and individual obstetricians and gynecologists are responsible for being involved in achieving SRHR.

Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Mortality and morbidity of extremely low birth weight infants in Japan, 2015.

BACKGROUND: In Japan, the mortality rate of extremely low birth weight (ELBW) infants is notably low in comparison with other developed countries, but the prevalence of chronic lung disease (CLD) and retinopathy of prematurity (ROP) is relatively high. This study aimed to estimate the mortality and morbidity of ELBW infants born in 2015 who were admitted to neonatal intensive care units (NICUs) in Japan and to examine the factors that affected the short-term outcomes of these infants. We also compared the mortality of ELBW infants born in 2005, 2010, and 2015. METHODS: We analyzed the mortality, morbidity, and factors related to short-term outcomes of ELBW infants, using data from 2782 infants born in 2015 and registered at NICUs in Japan. RESULTS: The mortality rates during NICU stays were 17.0%, 12.0%, and 9.8% for ELBW infants born in 2005, 2010, and 2015, respectively. Among ELBW infants born in 2015, multiple logistic regression analysis showed that short gestational age and low birthweight Z-score contributed to the increased risk of death. Births by cesarean section and antenatal corticosteroid administration were significantly associated with a reduced risk of death. Among infants who survived, CLD was observed in 53.1% and ROP requiring treatment was observed in 30.4%. CONCLUSIONS: Mortality in ELBW infants decreased significantly from 2005 to 2015. As CLD and ROP may affect quality of life and long-term outcomes of infants who survived, prevention strategies and management for these complications are critical issues in neonatal care in Japan.

Is there a need for a technical certification system for gynecological robotic surgery? Questionnaire survey of members of the Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy.

The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy (JSGOE) introduced a system for the certification of laparoscopic surgeons in 2002 and a system for the certification of facilities in 2014. We examined the opinions of the members of the Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy (JSGOE) regarding the necessity of a certification training system and a technical certification system for robotic surgery skills in Japan. Members of the JSGOE were surveyed with two questionnaires. Overall, 870 and 519 participants responded to the first and second questionnaires, respectively. Half of the respondents indicated that both systems were necessary. The breakdown by age and qualifications showed that this was especially true for the younger generation and respondents with more experience with robotic surgery. Overall, 40% of the respondents judged that a certification system for robotic surgery alone (with or without certification in laparoscopic surgery but with a requirement of experience in laparoscopic surgery) would be necessary. The opinions of the JSGOE members on making a certification system for robotic surgery were split into two clear-cut camps. Thus, we must further seek the extent of public demand for using a public survey so that a final decision can be made on whether to establish this system.

Effects of localisation of uterine adenomyosis on outcome of in vitro fertilisation/intracytoplasmic sperm injection fresh and frozen-thawed embryo transfer cycles: a multicentre retrospective cohort study.

BACKGROUND: Uterine adenomyosis is a benign disease, common among women in their 40 and 50 s, characterised by ectopic endometrial tissue in the uterine myometrial layer. Adenomyosis causes infertility and has a negative effect on the outcomes of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer (ET) cycles. It has also been reported to have different characteristics depending on the adenomyotic lesion localisation. The effect of its localisation on IVF/ICSI-ET outcomes is unclear. This study aimed to investigate whether adenomyotic lesion localisation, assessed using magnetic resonance imaging (MRI), was associated with outcomes of IVF/ICSI-ET cycles. METHODS: This multicentre, joint, retrospective cohort study analysed the medical records of 67 infertile patients with adenomyosis who underwent IVF/ICSI with fresh and frozen-thawed ET at five participating facilities from January 2012 to December 2016 and for whom MRI data were available. Fifteen patients were excluded; therefore, the MRI data of 52 patients were evaluated by two radiologists. We assessed the localisation of and classified adenomyotic lesions into advanced (invades the full thickness of the uterine myometrium), extrinsic (localised on the serosal side), and intrinsic (localised on the endometrial side) subtypes. RESULTS: There were 40 advanced, nine extrinsic, and three intrinsic cases, and the outcomes of 100, 27, and nine ET cycles, respectively, were analysed. Pregnancy loss/clinical pregnancy and live birth rates of the advanced, extrinsic, and intrinsic groups were 64 % (16/25) and 9 % (9/100), 33.3 % (3/9) and 22.2 % (6/27), and 50 % (1/2) and 11.1 % (1/9), respectively. A logistic regression analysis adjusted for age, prior miscarriage, and body mass index showed that the extrinsic group had fewer pregnancy losses (odds ratio 0.06; 95 % confidence interval [CI]: 0.00-0.54, p = 0.026) and more live births (odds ratio 6.05; 95 % CI: 1.41-29.65, p = 0.018) than the advanced group. CONCLUSIONS: Adenomyotic lesions exert different effects on IVF/ICSI-ET outcomes. Thus, MRI assessments of adenomyosis in infertile patients are beneficial. Establishment of treatment plans based on adenomyotic lesion localisation should be considered.

A semen-based stimulation method to analyze cytokine production by uterine CD56bright natural killer cells in women with recurrent pregnancy loss.

Cytokine secretion by NK cells is abnormal in some women with recurrent pregnancy loss (RPL). Cytokine production is usually evaluated after stimulation with PMA and ionomycin. However, stimulation of uterine NK cells with semen corresponds more closely to physiological conditions at the time of conception. As seminal plasma has immunomodulatory properties, we aimed to elucidate compatibility between uterine NK cells and semen. Endometrial samples were stimulated with PMA/ionomycin, semen, seminal plasma, or spermatozoa. Thereafter, cytokine production by NK (CD56bright) cells was evaluated using flow cytometry and compared between women with and without a history of RPL associated with abnormal NK cell distribution in the endometrium or unexplained RPL. The ratios (%) of NK cells producing IFN-γ and TNF-α (NK1 phenotype), IL-4 (NK1/NK2 phenotype), and IL-10 (NK1/NKr1 phenotype) were significantly lower after stimulation with semen than with PMA/ionomycin (P < 0.01). After exposure to semen, ratios (%) of NK cells producing IL-4 and IL-10 in patients with unexplained RPL were significantly lower (P < 0.05), whereas those of NK1/NK2 and NK1/NKr1 were significantly higher (P < 0.01) than those in controls. The shift of endometrial NK cells to the NK2 phenotype was more pronounced when stimulated by semen than by PMA/ionomycin. However, a semen-induced shift to NK1 in women with unexplained RPL could induce miscarriage. Couple-specific immunological compatibility tests through semen stimulation in vitro might provide important information to avoid RPL.

Differences in semen characteristics between patients with testicular cancer and other malignancies using various cut-off values.

OBJECTIVES: To compare semen parameters between patients with testicular cancer and other malignancies using various cut-off values, and to evaluate the correlation between semen parameters and intracytoplasmic sperm injection outcomes. METHODS: We retrospectively investigated semen parameters before cancer treatment in 117 patients with malignancies who cryopreserved sperm at Hirosaki University Hospital between November 1999 and May 2016. We compared semen parameters between patients with testicular cancer and other malignancies (non-testicular cancer), seminoma and non-seminoma, and stage I testicular cancer and stage II/III testicular cancer. The assessment of cut-off values recommended by the World Health Organization and the total motile sperm count was carried out between the testicular cancer and non-testicular cancer groups. The intracytoplasmic sperm injection outcomes in those using preserved sperm were assessed. RESULTS: Of the 111 patients enrolled, 29 (26%) had testicular cancer and 82 (74%) had non-testicular cancer. Patients with testicular cancer showed significantly lower total sperm concentration than non-testicular cancer patients. The cut-off value of total sperm concentration distinguished the patient proportions exceeding the cut-off between patients with testicular cancer (41%) and non-testicular cancer (66%). The comparison between patients with seminoma versus non-seminoma and stage I versus stage II/III testicular cancer presented no significant differences in semen parameters. No correlation between pretreatment semen parameters and intracytoplasmic sperm injection outcomes was observed. CONCLUSIONS: Although testicular cancer patients show lower total sperm concentration, intracytoplasmic sperm injection outcomes are acceptable. Further studies on the fertility potential of testicular cancer patients are warranted.

Onco-testicular sperm extraction (Onco-TESE) from a single testis with metachronous bilateral testicular cancer: a case report.

BACKGROUND: Although oncologic testicular sperm extraction (onco-TESE) has been increasingly practiced, the evidence of onco-TESE performed in patients with testicular cancer is insufficient. Furthermore, in bilateral testicular cancer, accounting for 0.5%-1% of testicular cancers, onco-TESE is more challenging and has been insufficiently reported. CASE PRESENTATION: Here we report the case of a 25-year-old man who underwent onco-TESE from his residual single testis with a nonseminomatous germ cell tumor that occurred 5 years after orchiectomy of the contralateral testis. A second orchiectomy and simultaneous TESE from the noncancerous testicular tissue were performed. The pathological diagnosis was germ cell tumors, tumors of more than one histological type (embryonal carcinoma, immature teratoma, yolk sac tumor, seminoma, and choriocarcinoma; pT1N0M0). The patient subsequently married and hoped for fatherhood 3 years later. Whereas histological diagnosis of the normal testicular tissue was Johnsen score 6 (maturation arrest), morphologically normal and motile sperms were successfully retrieved from thawed TESE samples and used for multiple cycles of intracytoplasmic sperm injection. Although the conception has not been succeeded to date, ICSI attempts have been continuing. CONCLUSION: This case demonstrates the effectiveness of onco-TESE for challenging cases such as bilateral and nonseminmatous testicular cancer.

CONTEXTE: Bien que l'extraction oncologique de spermatozoïdes testiculaires (onco-TESE) soit une pratique croissante, le bien-fondé de réaliser une onco-TESE chez des patients qui ont un cancer du testicule reste insuffisamment étayé. Par ailleurs, en cas de cancer bilatéral, qui représente 0,5­1% des cancers du testicule, l'onco-TESE est. plus difficile, et peu de cas ont été rapportés. CAS CLINIQUE: Nous rapportons le cas d'un homme de 25 ans qui a bénéficié d'une onco-TESE pour tumeur à cellules germinales non séminomateuse sur testicule unique résiduel, survenant 5 ans après une orchidectomie controlatérale. Ont été réalisées simultanément une seconde orchidectomie et une TESE sur tissu testiculaire non tumoral. L'étude anatomopathologique a montré des tumeurs à cellules germinales de plus d'un type histologique (carcinome embryonnaire, tératome immature, tumeur vitelline, séminome, et choriocarcinome; pT1N0M0). Le patient a ensuite convolé en noces et le couple a souhaité avoir un enfant 3 ans plus tard. Alors que l'étude histologique du tissu testiculaire normal donnait un score de Johnsen à 6 (arrêt de maturation), des spermatozoïdes morphologiquement normaux et mobiles ont été retrouvés dans les échantillons de TESE décongelés; ces spermatozoïdes ont été utilisés pour réaliser plusieurs cycles d'injection intra cytoplasmique. Bien qu'aucune conception n'ait eu lieu à ce jour, les tentatives d'ICSI se poursuivent. CONCLUSIONS: Ce cas montre l'efficacité de l'onco-TESE face à des cas tels qu'un cancer testiculaire bilatéral et non séminomateux.

Expression of natural cytotoxicity receptors and cytokine production on endometrial natural killer cells in women with recurrent pregnancy loss or implantation failure, and the expression of natural cytotoxicity receptors on peripheral blood natural killer cells in pregnant women with a history of recurrent pregnancy loss.

AIM: Natural cytotoxicity receptors (NCR) are unique markers that regulate natural killer (NK) cell cytotoxicity and cytokine production. In this study, we investigated the expression of NCR (NKp46, NKp44, and NKp30) and cytokine production in NK cells derived from the uterine endometrium of women with recurrent pregnancy loss (RPL). We also investigated the expression of NCR in peripheral blood NK cells in pregnant women with and without a history of RPL. METHODS: The expression of NCR (NKp46, NKp44, and NKp30) in NK cells (CD56dim and CD56bright ) in the uterine endometrium was analyzed using 3-color flow cytometry. Cytokine (tumor necrosis factor-α and interferon-γ) production was also analyzed. NK cells from the mid-secretory endometrium of 28 women with RPL, 34 women with implantation failure, and 74 controls were collected and mechanically dispersed using a tissue grinder. The expression of NCR in peripheral blood NK cells from pregnant women with (n = 17) and without (n = 91) a history of RPL was analyzed. RESULTS: The percentages of NKp46+ NK cells were significantly lower in both women with RPL and pregnant women with a history of RPL. The percentages of tumor necrosis factor-α- and/or interferon-γ-producing uterine endometrial NK cells were significantly lower in women with RPL compared with controls. CONCLUSION: The changes in NCR expression and cytokine production, especially decreased NKp46 expression in endometrial NK cells, suggests the presence of abnormal NK cell regulation in women with reproductive failures.

A case of bilateral tubal pregnancy.

Bilateral tubal pregnancy is very rare and occurs in only 1 out of every 200,000 spontaneous pregnancies. In this case, a 29-year-old woman with a history of primary infertility underwent treatment with human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG), and became pregnant. A gestational sac (GS) was not detected in the uterus and transvaginal ultrasonography (USG) revealed GS with fetal heartbeat in the left adnexa at 7 weeks and 6 days of gestation. The patient underwent laparoscopic surgery and ultimately, bilateral tubal pregnancy was diagnosed. Consequently, bilateral fallopian tube resection was performed. Afterwards, she conceived by assisted reproductive technology (ART) and delivered vaginally. This case suggests that even if a GS is found in one fallopian tube by USG, it is important to evaluate the other fallopian tube carefully. Abbreviations: TV-USG, transvaginal ultrasound; hCG, human chorionic gonadotropin; DD, dichorionic-diamniotic.

Expression of retinoid-related orphan receptor (ROR)γt on NK22 cells in the peripheral blood and uterine endometrium of women with unexplained recurrent pregnancy loss and unexplained infertility.

AIM: Recently, NK22 cells, a subset of interleukin (IL)-22-producing natural killer (NK) cells, were identified. We have previously reported the higher percentage of NK22 cells in women suffering recurrent pregnancy loss (RPL). Moreover, we have also reported lower expression of NKp46, a kind of natural cytotoxicity receptor (NCR), on NK cells and the changes of NK cell producing cytokines in women who experience RPL. NK22 cells express NCRs, such as NKp44 or NKp46. Retinoid-related orphan receptor γt (RORγt) is known as a regulator of NK22 cells; however, in NK22 cells of peripheral blood (PB) and the uterine endometrium (UE), the relationship between NCRs and RORγt is unclear. We investigate RORγt expression NK22 cells in the PB and UE of women with unexplained infertility (uI) or unexplained RPL (uRPL). METHODS: Lymphocytes were extracted from PB and UE, derived from women with uI or uRPL. Expression of RORγt and NCRs in NK cells and NK cell-produced cytokines were analyzed by flow cytometry. RESULTS: CD56+ /NKp46+ /RORγt+ cells were positively correlated with CD56+ /IL-22+ cells in both PB and UE. CD56bright /NKp46bright /RORγt+ cells were significantly higher in uRPL than in uI, and endometrial CD56bright /NKp46bright /RORγt+ cells were positively correlated with PB. In UE, CD56bright /RORγt+ cells were negatively correlated with CD56bright /interferon-γ+ and CD56bright /tumor necrosis factor-α+ cells of uRPL. CONCLUSION: RORγt may be associated with NK22 cells in reproduction. Particularly, higher expression of RORγt may be associated with elevated NK22 cells in uRPL.

NK22 Cells in the Uterine Mid-Secretory Endometrium and Peripheral Blood of Women with Recurrent Pregnancy Loss and Unexplained Infertility.

PROBLEM: We aimed to investigate natural killer 22 (NK22) cells in the peripheral blood and the uterine endometrium of women with unexplained recurrent pregnancy loss (URPL) and unexplained infertility (UI). METHOD OF STUDY: Peripheral blood and endometrial samples were collected from women with URPL (n = 43) and UI (n = 38). Intracellular cytokine production, such as IL-22, IFN-γ and TNF-α, and the expression of NKp46 on NK cells were analyzed by three-color flow cytometry. RESULTS: The percentages of endometrial CD56(+) /IL-22(+) and CD56(dim) /IL-22(+) cells in women with URPL were significantly higher than those of UI (P < 0.05, respectively). In addition, the percentage of CD56(bright) /IL-22(+) cells in women with RPL was negatively correlated with those of CD56(bright) /IFN-γ(+) and CD56(bright) /TNF-α(+) in both peripheral blood and endometrial NK cells. This was not seen in women with UI. The percentage of CD56(bright) /IL-22(+) cells was negatively correlated with CD56(bright) /NKp46 expressing NK cells in peripheral blood. CONCLUSION: Endometrial NK22 cells are differently regulated in women with URPL and UI. Women with URPL have higher level of NK22 cells with a potential to induce NK2 shift than women with UI.

Expression of natural cytotoxicity receptors on peritoneal fluid natural killer cell and cytokine production by peritoneal fluid natural killer cell in women with endometriosis.

PROBLEM: To investigate the relationship between the expression of natural cytotoxicity receptors (NCRs) on peritoneal fluid (PF) natural killer (NK) (pfNK) cells and cytokine production by pfNK cells in women with endometriosis. METHOD OF STUDY: Peritoneal fluid was collected from women with endometriosis undergoing laparoscopic surgery (n = 21) and controls without endometriosis (n = 28). The expression of NK cell surface antigens such as CD16 and NCRs (NKp46, NKp44 and NKp30) on pfNK cells, and cytokines production by pfNK cells [tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, GM-CSF and transforming growth factor (TGF)-ß1] were measured using multicolor flow cytometry. RESULTS: The percentages of CD56(+)/NKp46(+) cells and CD56(dim) /NKp46(+) cells in severe endometriosis group were significantly lower than that in controls. TNF-α and IFN-γ production by pfNK cells in severe endometriosis group was significantly higher than those in controls. CONCLUSION: The differential expression of NKp46, TNF-α, and IFN-γ on pfNK cells in women with severe endometriosis may allow the proliferation and angiogenesis of endometriotic cells.

Role of NKp46 expression in cytokine production by CD56-positive NK cells in the peripheral blood and the uterine endometrium.

PROBLEM: To investigate the role of natural cytotoxicity receptor, NKp46 expression in cytokine-producing NK cells. METHOD OF STUDY: CD56(+) /NKp46(+) NK cells from the peripheral blood and the uterine endometrium were magnetically separated. IFN-γ, TNF-α, IL-4, IL-10, and TGF-ß(1) expressions on NK cells were investigated using multicolor flow cytometry. RESULTS: Peripheral blood and uterine endometrial NK cells were grouped into 4 subpopulations based upon the degree of CD56 and NKp46 expressions. NKp46 expression was associated with higher frequency of cytokine-producing NK cells, including CD56(dim) NK cells. The percentage of TNF-α(+) and IL-10(+) NK cells per total CD56(+) /NKp46(+) NK cells in the uterine endometrium showed a significant correlation with those of the peripheral blood in all subpopulations, but that of IFN-γ(+) , IL-4(+,) and TGF-ß(1) (+) NK cells showed partial correlation. CONCLUSION: Expression of NKp46 is involved in cytokine production of CD56(+) NK cells in the peripheral blood and the uterine endometrium.

Retinoic acid-inducible gene-I is induced by interferon-gamma and regulates CXCL11 expression in HeLa cells.

Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH box family proteins, which have diverse roles in the regulation of gene expression and cellular functions. RIG-I is one of the factors regulated by interferon (IFN)-gamma and regarded as an intracellular signaling molecule for IFN-gamma. IFN-gamma is a major cytokine and also suggested to be involved in embryonal implantation and pregnancy. It is demonstrated that IFN-gamma stimulates endometrial epithelial cells to produce CXCL11, which is implicated in implantation. The aim of the present study was to investigate the effect of IFN-gamma on RIG-I expression in HeLa cells, a cell line derived from human uterine carcinoma. We found that RIG-I mRNA and protein were expressed in HeLa cells stimulated with IFN-gamma. The effect of IFN-gamma was observed in concentration- and time-dependent manners. The RNA interference against RIG-I resulted in the suppression of the IFN-gamma-induced CXCL11 expression. Immunohistochemical studies revealed the RIG-I expression in the normal human endometrium, suggesting a possible role of RIG-I in human reproductive organs.