Preimplantation genetic testing using comprehensive genomic copy number analysis is beneficial for balanced translocation carriers.

Balanced chromosomal translocation is one of chromosomal variations. Carriers of balanced chromosomal translocations have an increased risk of spontaneous miscarriage. To avoid the risk, preimplantation genetic testing (PGT) using comprehensive genomic copy number analysis has been developed. This study aimed to verify whether and how embryos from couples in which one partner is a balanced translocation carrier have a higher ratio of chromosomal abnormalities. A total of 894 biopsied trophectoderms (TEs) were obtained from 130 couples in which one partner was a balanced translocation carrier (Robertsonian translocation, reciprocal translocation, or intrachromosomal inversion) and grouped as PGT-SR. Conversely, 3269 TEs from 697 couples who experienced recurrent implantation failure or recurrent pregnancy loss were included in the PGT-A group. The transferable blastocyst ratio was significantly lower in the PGT-SR group, even when bias related to the sample number and patient age was corrected. Subgroup analysis of the PGT-SR group revealed that the transferable blastocyst ratio was higher in the Robertsonian translocation group. Because the PGT-SR group had a higher proportion of untransferable embryos than the PGT-A group, PGT using comprehensive genomic copy number analysis was more beneficial for balanced translocation carriers than for infertility patients without chromosomal translocations. The frequencies of de novo aneuploidies were further analyzed, and the frequency in the PGT-SR group was lower than that in the PGT-A group. Therefore, we could not confirm the existence of interchromosomal effects in this study.

Use of clinical variables for preoperative prediction of lymph node metastasis in endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common gynaecological cancer, and most patients are identified during early disease stages. Noninvasive evaluation of lymph node metastasis likely will improve the quality of clinical treatment, for example, by omitting unnecessary lymphadenectomy. METHODS: The study population comprised 611 patients with endometrial cancer who underwent lymphadenectomy at four types of institutions, comprising seven hospitals in total. We systematically assessed the association of 18 preoperative clinical variables with postoperative lymph node metastasis. We then constructed statistical models for preoperative lymph node metastasis prediction and assessed their performance with a previously proposed system, in which the score was determined by counting the number of high-risk variables among the four predefined ones. RESULTS: Of the preoperative 18 variables evaluated, 10 were significantly associated with postoperative lymph node metastasis. A logistic regression model achieved an area under the curve of 0.85 in predicting lymph node metastasis; this value is significantly higher than that from the previous system (area under the curve, 0.74). When we set the false-negative rate to ~1%, the new predictive model increased the rate of true negatives to 21%, compared with 6.8% from the previous one. We also provide a spreadsheet-based tool for further evaluation of its ability to predict lymph node metastasis in endometrial cancer. CONCLUSIONS: Our new lymph node metastasis prediction method, which was based solely on preoperative clinical variables, performed significantly better than the previous method. Although additional evaluation is necessary for its clinical use, our noninvasive system may help improve the clinical treatment of endometrial cancer, complementing minimally invasive sentinel lymph node biopsy.

A nationwide survey of the use of the laparoscopic power morcellator.

AIM: Laparoscopic power morcellator (LPM) can be used for tissue retrieval through laparoscopic port site, but the dissemination of uterine and/or myoma tissues is a serious complication. To study the use of LPM for uterine fibroid treatment in Japan, we aimed to perform two national cross-sectional surveys comprising multiple questionnaires. METHODS: The first survey (2011-2013) was conducted in November 2014, and 203 medical institutions responded. The second survey (2017-2019) was conducted in December 2020, and 302 medical institutions were investigated. RESULTS: Overall, 72 104 and 120 425 surgeries and 0.04% and 0.05% cases of postoperative malignancy diagnosis were reported in the first and second surveys, respectively. Magnetic resonance imaging was performed in >90% of the cases in the first and second surveys as preoperative examinations. The frequency of LPM at hysterectomy was 8.9% and 4.6% and the frequency of LPM at laparoscopic myomectomy was 80.4% and 54.8% in the first and second surveys, respectively; both the parameters decreased in the second survey. CONCLUSIONS: It is impossible to completely exclude malignant diseases even if extensive preoperative diagnosis has been done before surgery. Therefore, the use of LPM in patients requires careful attention and informed consent in Japan.

Comparison of 1-year cumulative live birth and perinatal outcomes following single blastocyst transfer with or without preimplantation genetic testing for aneuploidy: a propensity score-matched study.

PURPOSE: We evaluated whether preimplantation genetic testing for aneuploidy (PGT-A) could increase the cumulative live birth rate (CLBR) in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL). METHODS: The clinical records of 7,668 patients who underwent oocyte retrieval (OR) with or without PGT-A were reviewed for 365 days and retrospectively analyzed. Using propensity score matching, 579 patients in the PGT-A group were matched one-to-one with 7,089 patients in the non-PGT-A (control) group. Their pregnancy and perinatal outcomes and CLBRs were statistically compared. RESULTS: The live birth rate per single vitrified-warmed blastocyst transfers (SVBTs) significantly improved in the PGT-A group in all age groups (P < 0.0002, all). Obstetric and perinatal outcomes were comparable between both groups regarding both RIF and RPL cases. Cox regression analysis demonstrated that in the RIF cases, the risk ratio per OR was significantly lower in the PGT-A group than in the control group (P = 0.0480), particularly in women aged < 40 years (P = 0.0364). However, the ratio was comparable between the groups in RPL cases. The risk ratio per treatment period was improved in the PGT-A group in both RIF and RPL cases only in women aged 40-42 years (P = 0.0234 and P = 0.0084, respectively). CONCLUSION: Increased CLBR per treatment period was detected only in women aged 40-42 years in both RIF and RPL cases, suggesting that PGT-A is inappropriate to improve CLBR per treatment period in all RIF and RPL cases.

Preimplantation genetic testing for aneuploidy and chromosomal structural rearrangement: A summary of a nationwide study by the Japan Society of Obstetrics and Gynecology.

Purpose: The Japan Society of Obstetrics and Gynecology conducted a nationwide clinical study to evaluate the pregnancy outcomes of preimplantation genetic testing for aneuploidy or chromosomal structural rearrangement (PGT-A/SR). Methods: Patients that had experienced recurrent implantation failure, recurrent pregnancy loss, or chromosomal structural rearrangement were recruited from 200 fertility centers in Japan. For patients in whom one or more blastocysts were classified as euploid or euploid with suspected mosaicism, a frozen-thawed single embryo transfer (ET) was performed. Results: A total of 10 602 cycles, maternal age 28-50 years, were enrolled in this study. 42 529 blastocysts were biopsied, and 25.5%, 11.7%, and 61.7% of embryos exhibited euploidy, mosaicism, and aneuploidy, respectively. At least one euploid blastocyst was obtained in 38.3% of egg retrieval cycles with embryo biopsy. A total of 6080 ETs were carried out, and the clinical pregnancy rate per ET, ongoing pregnancy rate per ET, and miscarriage rate per pregnancy were 68.8%, 56.3%, and 10.4%, respectively. The rates of clinical pregnancy and miscarriage remained relatively constant across all maternal ages. Conclusions: Preimplantation genetic testing for aneuploidy or chromosomal structural rearrangement may improve the pregnancy rate per ET and reduce the miscarriage rate per pregnancy, especially in patients of advanced maternal age.

Maternal cell contamination in embryonic chromosome analysis of missed abortions.

AIM: The fetal sample used for embryonic chromosome analysis is often contaminated with maternal cells, making it difficult to evaluate the fetal chromosomes. We examined on the rate of maternal cell contamination and its relationship with maternal information in the embryonic chromosome analysis of missed abortions using the Giemsabanding method. METHODS: Chromosome analysis was performed in 200 cases of delayed miscarriages in first trimester between July 1, 2000 and May 31, 2019. Chorionic villi were collected and were analyzed using the Giemsa banding method. Among the 20 cells for which chromosomal examination was performed, cells wherein 46,XX chromosomes were found together with normal male karyotype or abnormal chromosomes were defined as maternal cell contamination. RESULTS: Of the 200 cases analyzed, 136 had abnormal chromosomes. The normal female karyotype (n = 52) was four times more prevalent than the normal male karyotype (n = 12). Maternal cell contamination was seen in 15.4% of the abnormal chromosome cases and 8.3% of the normal male karyotype cases. There was no significant difference in the gestational age between the contaminated and noncontaminated groups at the time of miscarriage diagnosis. However, miscarriage before fetal heartbeat confirmation was significantly associated with higher maternal cell contamination. CONCLUSION: We found maternal cell contamination in 15% of all the cases. Moreover, in many cases of the normal female karyotype, it was suspected that only maternal chromosomes were cultured. When performing embryonic chromosome analysis in recurrent miscarriages, we should pay attention to maternal cell contamination and interpret the results accordingly.

Upregulated serum granulysin levels in women with antiphospholipid antibody-associated recurrent miscarriage are downregulated by heparin treatment.

Purpose: Granulysin is a cytotoxic protein that simultaneously activates innate and cellular immunity. The authors aimed to evaluate whether granulysin is associated with the antiphospholipid antibody syndrome and whether heparin changes the granulysin levels. Methods: A cohort study was performed with women with antiphospholipid antibody-positive recurrent pregnancy loss (RPL). The authors examined granulysin levels under RPL and evaluated the changes in serum granulysin levels before and 1 week after the commencement of heparin treatment. Results: Serum granulysin levels before heparin treatment were significantly higher in women who tested positive for one or more types of antiphospholipid antibodies (2.75 ± 1.03 vs. 2.44 ± 0.69, p = 0.0341 by Welch's t test), particularly anti-phosphatidylethanolamine antibodies (IgG: 2.98 ± 1.09 vs. 2.51 ± 0.86, p = 0.0013; IgM: 2.85 ± 1.09 vs. 2.47 ± 0.77, p = 0.0024 by Welch's t test). After heparin treatment for 1 week, serum granulysin levels were significantly reduced (p = 0.0017 by the paired t test). The miscarriage rate was significantly higher in women whose serum granulysin levels were not reduced by heparin treatment (p = 0.0086 by Fisher's exact probability test). Conclusion: The results suggest that heparin may reduce the incidence of miscarriage by suppressing serum granulysin levels.

Use of tumor markers to distinguish endometriosis-related ovarian neoplasms from ovarian endometrioma.

OBJECTIVE: Only few studies have focused on tumor markers used in the preoperative diagnosis of endometriosis-related ovarian neoplasms, and previous studies have only assessed serum CA125 levels. This study investigated the significance of preoperative tumor markers and clinical characteristics in distinguishing endometriosis-related ovarian neoplasms from ovarian endometrioma. METHODS: A case-control study was conducted on 283 women who were diagnosed with confirmed pathology with endometriosis-related ovarian neoplasms (n=21) and ovarian endometrioma (n=262) at a single institution from April 2008 to April 2018. The serum CA125, CA19-9, carcinoembryogenic antigen (CEA), sialyl Lewis-x antigen (SLX), and lactate dehydrogenase (LDH) levels, age, tumor size, and the presence of mural nodule of the patients were analyzed. RESULTS: Patients with endometriosis-related ovarian neoplasms were more likely to be older (48 (range, 26-81) vs 39 (range, 22-68) years, P<0.001), have higher levels of CA19-9 (42 vs 19 U/mL, P=0.013), CEA (1.3 vs 0.84 ng/mL, P=0.007), SLX (41 vs 33 U/mL, P=0.050), and LDH (189 vs 166 U/mL, P<0.001) and larger tumor size (79 vs 55 mm, P=0.001), and present with mural nodule (85.7 vs 4.5 %, P<0.001) than those with ovarian endometrioma. The CA125 levels did not significantly differ between the two groups. The area under the curve for each factor was as follows: CA19-9 level, 0.672 (95% CI 0.52 to 0.83; P=0.013); CEA level, 0.725 (95% CI 0.58 to 0.87; P=0.007); SLX level, 0.670 (95% CI 0.53 to 0.84; P=0.050); LDH level, 0.800 (95% CI 0.70 to 0.90; P<0.001); age, 0.775 (95% CI 0.65 to 0.90; P<0.001); and tumor size, 0.709 (95% CI 0.56 to 0.86; P=0.001). Age was a better marker than CA19-9, CEA, and SLX levels according to the receiver operating characteristic curve analysis. The optimal cut-off values for age and tumor size were 47 years and 80 mm, respectively. CONCLUSIONS: The assessment of serum CA19-9, CEA, SLX, and LDH levels may be a useful tool in the preoperative evaluation to differentiate between endometriosis-related ovarian neoplasms and ovarian endometrioma.

Recurrence of uterine adenomyosis after administration of gonadotropin-releasing hormone agonist and the efficacy of dienogest.

This study elucidated the degree of adenomyosis recurrence following gonadotropin-releasing hormone agonist (GnRHa) discontinuation and dienogest efficiency for recurrent adenomyosis. This retrospective cohort study included 30 patients, divided into a group of patients whose progress was observed without providing additional therapy following GnRHa administration for six months (Group G) and a group of patients administered dienogest for six months following six months of GnRHa administration (Group D). Menorrhagia, dysmenorrhea, chronic pelvic pain, abdominal fullness, and uterine volume were recorded prior to treatment, six months after the start of therapy (6 M), and 12 months after the start of therapy (12 M). In Group G (n = 15), although all subjective symptoms disappeared at 6 M, nearly all symptoms recurred at 12 M. Uterine volume significantly decreased from 341.0 cm3 to 156.0 cm3 at 6 M (p = .001) and significantly increased again to 282.3 cm3 at 12 M (p = .003). In Group D (n = 15), all subjective symptoms disappeared at 6 M, and only abdominal fullness returned in a significant number of patients (5 of 5; p = .021) at 12 M. Uterine volume decreased significantly at 6 M (p = .003) and significantly increased again from 162.5 cm3 to 205.6 cm3 at 12 M (p = .006). Subjective symptoms, except for abdominal fullness, did not recur when dienogest was administered after GnRHa.

Accuracy and clinical value of an adhesion scoring system: A preoperative diagnostic method using transvaginal ultrasonography for endometriotic adhesion.

AIM: To investigate the accuracy and clinical value of an adhesion scoring system using transvaginal ultrasonography for endometriotic adhesion. METHODS: In this prospective observational study, we included 131 patients with endometriosis who underwent surgery. Before surgery, transvaginal ultrasonography and adhesion mapping were performed to determine the presence or absence of adhesions at 10 sites of the pelvis. Mapping accuracy was determined by comparing the mapping findings with the surgical findings. To determine the severity of pelvic adhesions, we developed an adhesion score (0-10). With the adhesion score, we assessed the effect of surgical adhesiolysis and evaluated the relationship between postoperative adhesions and infertility. RESULTS: Of the 10 sites assessed for adhesions, the most frequent site of adhesions was the site between the left ovary and the uterus (70.5%). The overall sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy of adhesion mapping were 80.4%, 86.1%, 78.8%, 87.2%, 5.79, 0.23 and 83.9%, respectively. The adhesion score in this system was significantly correlated with the adhesion-related score in the revised American Society for Reproductive Medicine classification (R2 = 0.734). Surgical adhesiolysis yielded only about 30% improvement postoperatively. The adhesion score 1 month after surgery in the non-in vitro fertilization (IVF) pregnancy group was significantly lower than that in the IVF pregnancy group (3.45 vs 5.21; P = 0.02). CONCLUSION: Our adhesion scoring system allowed an accurate prediction of the pelvic adhesion status and may potentially be an indicator of postoperative adhesions and infertility.

Expression level of long noncoding RNA H19 of normotensive placentas in late pregnancy relates to the fetal growth restriction.

AIM: Infants with fetal growth restriction (FGR) are at an increased risk of perinatal morbidity and mortality. The long noncoding RNA H19 gene is expressed abundantly in placental villi and recent studies suggest that it regulates FGR. However, the role of H19 in the FGR placenta remains unclear. This study aimed to clarify the relationship between H19 expression and FGR using normotensive placentas after 34 weeks of gestation. METHODS: Formalin-fixed paraffin-embedded tissues from human placentas collected from pregnancies resulting in small for gestational age (SGA) and appropriate for gestational age (AGA) newborns were used. The histopathological features of placenta tissues, such as villous stromal fibrosis, the numbers of terminal villi, villous vessels and cytotrophoblasts were analyzed using hematoxylin and eosin, Masson's trichrome staining and immunostaining. The localization and expression of H19 in the placentas were demonstrated by in situ hybridization and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Moreover, the expression levels of H19-regulated molecules such as IGF2 and decorin (DCN) were measured by RT-qPCR. RESULTS: Histopathological features of the placental villous were not different between placentas associated with SGA and AGA. H19 localized to the villous stroma, endothelial cells and cytotrophoblasts. Moreover, the expression level of H19 in SGA placentas was significantly lower than that in AGA placentas. The expression levels of IGF2 and DCN in SGA placentas tended to be lower than those in AGA placentas similarly to H19. CONCLUSION: This study highlights the potential importance of regulatory events mediated by H19 in SGA placentas without histopathological abnormalities in late pregnancy.

Infertility treatment hinders the careers of working women in Japan.

AIM: Women undergoing infertility treatment often need to balance work and fertility treatment. Therefore, we evaluated the quality of life (QOL) and impact of infertility treatment on Japanese working women and their careers. METHODS: We conducted an online questionnaire at 18 clinics in Japan. Responses were collected from 835 women, 713 of whom were working. The participants were divided into three groups based on treatment stage. Data were collected using the FertiQoL and an original questionnaire created by the authors. The Mann-Whitney U test and a multinomial logistic analysis were used. RESULTS: Approximately 90% of the participants felt that treatment could hinder their work and 8% had quit their jobs. Low QOL was associated with sadness and despair due to infertility and mood disorders, disruptions to life and work, and the complicated medications and procedures involved in treatment. Social isolation and the effect of fertility treatment on daily life and work strongly hindered the careers of working women in the third stage of treatment (in vitro fertilization and intracytoplasmic sperm injection). Approximately 70% of the participants required support to subsidize treatment costs and sought shorter working hours and flextime systems. Only 55% informed their workplaces about the fertility treatment, but about 70% easily gained understanding by informing them. CONCLUSIONS: For many working women, infertility treatment posed barriers to their careers, which could explain the low QOL. Urgent introduction of a support system is necessary in Japan, and understanding and social acceptance of infertility appears to be important.

Case of ovarian steroid cell tumor diagnosed after presenting acute heart failure.

We report a rare case of an ovarian steroid cell tumor with a diagnosis prompted by heart failure symptoms. A 28-year-old Japanese nulligravida/nullipara with a chief complaint of respiratory discomfort during physical exertion and exhibiting heart failure symptoms was referred to our hospital. She also had signs of virilization, including secondary menorrhea since the age of 20, hirsutism and balding. Cushing's syndrome was suspected, and further examinations showed hypertestosteronemia and right ovarian tumor. Symptomatic treatment for heart failure with diuretics and antihypertensives was followed by abdominal right adnexectomy performed due to the androgen-producing ovarian tumor. The tumor was solid and larger than a fist, and confirmed as a steroid cell tumor through postoperative histopathology. Serum total testosterone levels normalized at day 3 postoperatively, and menstruation resumed 2 months later. Our case was diagnosed due to heart failure symptoms, and its treatment resulted in improvement in virilization signs.

Miscarriage induced by adoptive transfer of dendritic cells and invariant natural killer T cells into mice.

Unexpected fetal loss is one of the common complications of pregnancy; however, the pathogenesis of many miscarriages, particularly those not associated with infections, is unknown. We previously found that activated DEC-205+ dendritic cells (DCs) and NK1.1+ invariant natural killer T (iNKT) cells are recruited into the myometrium of mice when miscarriage is induced by the intraperitoneal administration of α-galactosylceramide (α-GalCer). Here we demonstrate that the adoptive transfer of DEC-205+ bone marrow-derived DCs cocultured with α-GalCer (DEC-205+ BMDCs-c/w-α-GalCer) directly induced marked fetal loss by syngeneic pregnant C57BL/6 (B6) mice and allogeneic mice (B6 (♀) × BALB/c (♂)), which was accompanied by the accumulation of activated iNKT cells in the myometrium. Further, the adoptive transfer of NK1.1+ iNKT cells obtained from B6 mice injected with α-GalCer facilitated miscarriages in syngeneic Jα18(-/-) (iNKT cell-deficient) mice. These results suggest that DEC-205+ DCs and NK1.1+ iNKT cells play crucial roles required for the initiation of fetal loss associated with stimulation by glycolipid antigens and sterile inflammation.

Preimplantation genetic testing for aneuploidy: a comparison of live birth rates in patients with recurrent pregnancy loss due to embryonic aneuploidy or recurrent implantation failure.

STUDY QUESTION: Can preimplantation genetic testing for aneuploidy (PGT-A) improve the live birth rate and reduce the miscarriage rate in patients with recurrent pregnancy loss (RPL) caused by an abnormal embryonic karyotype and recurrent implantation failure (RIF)? SUMMARY ANSWER: PGT-A could not improve the live births per patient nor reduce the rate of miscarriage, in both groups. WHAT IS KNOWN ALREADY: PGT-A use has steadily increased worldwide. However, only a few limited studies have shown that it improves the live birth rate in selected populations in that the prognosis has been good. Such studies have excluded patients with RPL and RIF. In addition, several studies have failed to demonstrate any benefit at all. PGT-A was reported to be without advantage in patients with unexplained RPL whose embryonic karyotype had not been analysed. The efficacy of PGT-A should be examined by focusing on patients whose previous products of conception (POC) have been aneuploid, because the frequencies of abnormal and normal embryonic karyotypes have been reported as 40-50% and 5-25% in patients with RPL, respectively. STUDY DESIGN, SIZE, DURATION: A multi-centre, prospective pilot study was conducted from January 2017 to June 2018. A total of 171 patients were recruited for the study: an RPL group, including 41 and 38 patients treated respectively with and without PGT-A, and an RIF group, including 42 and 50 patients treated respectively with and without PGT-A. At least 10 women in each age group (35-36, 37-38, 39-40 or 41-42 years) were selected for PGT-A groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients and controls had received IVF-ET for infertility. Patients in the RPL group had had two or more miscarriages, and at least one case of aneuploidy had been ascertained through prior POC testing. No pregnancies had occurred in the RIF group, even after at least three embryo transfers. Trophectoderm biopsy and array comparative genomic hybridisation (aCGH) were used for PGT-A. The live birth rate of PGT-A and non-PGT-A patients was compared after the development of blastocysts from up to two oocyte retrievals and a single blastocyst transfer. The miscarriage rate and the frequency of euploidy, trisomy and monosomy in the blastocysts were noted. MAIN RESULT AND THE ROLE OF CHANCE: There were no significant differences in the live birth rates per patient given or not given PGT-A: 26.8 versus 21.1% in the RPL group and 35.7 versus 26.0% in the RIF group, respectively. There were also no differences in the miscarriage rates per clinical pregnancies given or not given PGT-A: 14.3 versus 20.0% in the RPL group and 11.8 versus 0% in the RIF group, respectively. However, PGT-A improved the live birth rate per embryo transfer procedure in both the RPL (52.4 vs 21.6%, adjusted OR 3.89; 95% CI 1.16-13.1) and RIF groups (62.5 vs 31.7%, adjusted OR 3.75; 95% CI 1.28-10.95). Additionally, PGT-A was shown to reduce biochemical pregnancy loss per biochemical pregnancy: 12.5 and 45.0%, adjusted OR 0.14; 95% CI 0.02-0.85 in the RPL group and 10.5 and 40.9%, adjusted OR 0.17; 95% CI 0.03-0.92 in the RIF group. There was no difference in the distribution of genetic abnormalities between RPL and RIF patients, although double trisomy tended to be more frequent in RPL patients. LIMITATIONS, REASONS FOR CAUTION: The sample size was too small to find any significant advantage for improving the live birth rate and reducing the clinical miscarriage rate per patient. Further study is necessary. WIDER IMPLICATION OF THE FINDINGS: A large portion of pregnancy losses in the RPL group might be due to aneuploidy, since PGT-A reduced the overall incidence of pregnancy loss in these patients. Although PGT-A did not improve the live birth rate per patient, it did have the advantage of reducing the number of embryo transfers required to achieve a similar number live births compared with those not undergoing PGT-A. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Japan Society of Obstetrics and Gynecology and grants from the Japanese Ministry of Education, Science, and Technology. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Is hysteroscopic metroplasty using the incision method for septate uterus a risk factor for adverse obstetric outcomes?

AIM: This study aimed to assess whether hysteroscopic metroplasty using the incision method for septate uterus is a risk factor for adverse obstetric outcomes during pregnancy or delivery. METHODS: This retrospective, single-center cohort study of obstetric complications included 41 patients with recurrent pregnancy loss or unexplained infertility who underwent hysteroscopic metroplasty using the incision method for septate uterus. As controls, we recruited 1139 women who delivered at our hospital during the same period. The primary outcomes were mean weeks of delivery, mean birthweight, rate of cesarean section, rate of breech presentation, rate of post-partum hemorrhage, rate of preterm delivery, rate of placental abruption, rate of placenta previa, rate of placenta accreta and uterine rupture during pregnancy and delivery. RESULTS: The two groups did not differ in terms of age, mean weeks of delivery, mean birthweight, rate of post-partum hemorrhage, rate of preterm delivery, rate of placental abruption, rate of placenta previa or rate of placenta accreta. The rates of cesarean section and breech presentation were significantly higher in the study group than in the control group (56.1 vs 27.7%; P = 0.0002 and 19.5 vs 6.8%; P = 0.007, respectively). There were no cases of uterine rupture during pregnancy or delivery following hysteroscopic metroplasty. CONCLUSION: Hysteroscopic metroplasty using the incision method for septate uterus is not a risk factor for adverse obstetric outcomes. No severe complications, such as placenta abruption, placenta previa, placenta accreta, uterine rupture or heavy hemorrhage, were observed in the postoperative live birth group.

Risk Factors and Outcomes of Recurrent Pregnancy Loss in Japan.

AIM: To clarify the risk factors and pregnancy outcomes for each risk factor of recurrent pregnancy loss (RPL) in Japan. METHODS: Using a prospective RPL database collected from 16 facilities in Japan, the prevalence of risk factors for RPL, their treatments and pregnancy outcomes were examined. RESULTS: Of 6663 patients registered in our database, 5708 patients had RPL. All examinations for risk factors were performed for 1340 patients (23.5%). The prevalences of positive antiphospholipid antibodies (aPL), malformation of the uterus, thyroid dysfunction, parental karyotype abnormality, factor XII deficiency, protein S deficiency and unknown risk factors were 8.7%, 7.9%, 9.5%, 3.7%, 7.6%, 4.3% and 65.1%, respectively. Although factor XII deficiency and protein S deficiency are not recognized as risk factors for RPL in general, low-dose aspirin (LDA) or unfractionated heparin + LDA therapy improved live birth rates. In transiently aPL-positive patients, the live birth rate with LDA therapy was similar to that with heparin + LDA. For unknown risk factors of RPL, the live birth rate in normal fetal karyotype in the none treatment group was similar to that in all other treatments group (81.3% vs 86.0%). Of 5708 RPL patients, pregnancy outcomes were known for 2261 patients and 1697 patients (75.1%) had at least one live birth. CONCLUSION: The risk factors and pregnancy outcomes for each risk factor of RPL are useful for clinicians and patients. Factor XII deficiency and protein S deficiency may be risk factors of RPL.

Cervical Dilatation Curves of Spontaneous Deliveries in Pregnant Japanese Females.

Background: Although cervical dilatation curves are crucial for appropriate management of labor progression, abnormal labor progression and obstetric interventions were included in previous and widely-used cervical dilatation curves. We aimed to describe the cervical dilatation curves of normal labor progression in pregnant Japanese females without abnormal labor progression and obstetric interventions. Methods: We completed retrospective obstetric record reviews on 3172 pregnant Japanese females (parity = 0, n = 1047; parity = 1, n = 1083; parity ≥ 2, n = 1042), aged 20 to 39 years old at delivery, with pregravid body mass indices of less than 30. All patients underwent spontaneous deliveries with term, singleton, cephalic and live newborns of appropriate-for-gestational age birthweight, without adverse neonatal outcomes. We characterized labor progression patterns by examining the relationship between elapsed times from the full dilatation and cervical dilatation stages, and labor durations by examining the distribution of time intervals from one cervical dilatation stage, to the next, and ultimately to the full dilatation. Results: Fastest cervical changes occurred at 6 cm (primiparas) and 5 cm (multiparas) of dilatation. The 95%tile of labor progression took over 3 hours to progress from 6 cm to 7 cm (primiparas), and over 2 hours to progress from 5 cm to 6 cm (multiparas). The 5%tile of traverse time to the full dilatation, during the active phase, was less than 1 hour (primiparas) and 0.5 hours (multiparas). At the end of the active phase, no deceleration phase was observed. Conclusions: Active labor may not start until 5 cm of dilatation. At the beginning of the active phase, cervical dilatation was slower than previously described. These results may reduce opportunities for obstetric interventions during labor progression.

Influence of perinatal low-dose acetylsalicylic acid therapy on fetal hemodynamics evaluated by determining the acceleration-time/ejection-time ratio in the ductus arteriosus.

AIM: Acceleration-time/ejection-time ratio (At/Et ratio) of Doppler waveform is an established hemodynamic parameters that reflect proximal stenosis. Using this parameter, we evaluated whether perinatal low-dose acetylsalicylic acid (ASA) therapy could alter hemodynamics in the ductus arteriosus. METHODS: Pulse Doppler measurements of the fetal ductus arteriosus were performed longitudinally from 20 to 37 gestational weeks in 106 healthy pregnant women (controls) and 65 pregnant women taking daily low-dose ASA (80 or 100 mg/day) because of a history of recurrent pregnancy loss. The At/Et ratio, pulsatility index (PI), and peak systolic velocity were evaluated and statistically analyzed. RESULTS: The At/Et ratio significantly increased with gestational age in both the ASA group (r = 0.54) and the control group (r = 0.35), while the PI did not. Median peak systolic velocities also increased with gestational age in both the ASA group (r = 0.39) and the control group (r = 0.31). No significant differences in At/Et ratio, PI, or peak systolic velocity were observed between the ASA group and the control group. CONCLUSION: Administration of low-dose ASA during pregnancy did not appear to alter hemodynamics in the fetal ductus arteriosus.

Innate immune cells in reproduction.

Fetomaternal immune tolerance is required to prevent fetal rejection during pregnancy; simultaneously, the maternal immune system must also protect the fetus from harmful endogenous and exogenous antigens, including those associated with viral and bacterial infections. Therefore, a delicate immune balance is critical for the maintenance of a successful pregnancy, while disruption of this balance can induce complications such as implantation failure, miscarriage, preterm birth/labor, preeclampsia and fetal growth restriction. While the adaptive immune system is critical for the development of tolerance, this review summarizes evidence that modulation of the innate immunity is also essential for achieving this delicate balance between tolerance and protection. Canonical cells of the innate immune system, including dendritic cells, macrophages, natural killer cells and invariant natural killer T cells, contribute to the modulation of the immune balance at the fetomaternal interface. The newly identified myeloid-derived suppressor cells and innate lymphoid cells also appear important for successful reproduction. Moreover, it is possible that sterile inflammation facilitates complications of pregnancy via the innate immune system. In this review, the characteristic features and functions of innate immune cells in fetomaternal immunity and their contributions to pregnancy complications related to sterile inflammation are discussed. These insights on innate immune system function in reproduction may provide new perspectives for understanding the mechanisms of fetomaternal tolerance and the etiology of pregnancy complications.