Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases.

BACKGROUND: The indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation. METHODS: We conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome. RESULTS: Forty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29-37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1-4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5-14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15-1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15-4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5-100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0-100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births. CONCLUSIONS: Oocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

Morphometric assessment of blastocysts: relationship with the ongoing pregnancy rate.

Objective: To explore a morphometric grading system for blastocysts that is associated with ongoing pregnancy. Design: Cross-sectional study. Setting: None. Patientss: All consecutive vitrified blastocysts at our center from July 2018 to November 2021 that were transferred in single blastocyst transfer cycles until January 2022. Interventions: None. Main Outcome Measures: The ongoing pregnancy rate after a single vitrified-warmed blastocyst transfer. Interobserver agreement on morphometric values among embryologists. Results: Three morphometric variables (blastocyst diameter, area of inner cell mass [ICM], and the estimated trophectoderm cell count) were used to evaluate the expansion, ICM, and trophectoderm morphology. During the study period, 585 blastocysts were involved in this study. Of the 3 morphometric variables, ICM area (per 500 µm2, adjusted odds ratio, 1.19; 95% confidence interval, 1.09-1.30) and estimated trophectoderm cell count (per 10 cells, adjusted odds ratio, 1.25; 95% confidence interval, 1.12-1.39) were significantly associated with the ongoing pregnancy rate after adjustment for confounding factors. The ongoing pregnancy rate was 2.0% (1/49) with an ICM area of <2,500 µm2 and the estimated trophectoderm cell count <70. The ongoing pregnancy rate reached 47.8% (22/46) when the ICM area and the estimated trophectoderm cell count were >3,500 µm2 and >110, respectively. Interobserver agreement on the blastocyst diameter, ICM area, and the estimated trophectoderm cell count was excellent-to-good among 5 embryologists (intraclass correlation coefficients: 0.99, 0.87, and 0.91, respectively). Conclusions: Morphometric values of ICM and trophectoderm are promising predictors of pregnancy success. The high reproducibility suggests that the morphometric variables will contribute to identifying blastocysts with the highest developmental potential as well as those that will not result in a successful pregnancy.

Embryonic ß-Catenin Is Required for Priming of the Uterus to Implantation.

Repeated implantation failure is a major cause of infertility among healthy women. Uterine ß-catenin (CTNNB1) plays a critical role in implantation. However, the role of embryonic CTNNB1 during implantation remains unclear. We addressed this topic by analyzing mice carrying Ctnnb1-deficient (Ctnnb1Δ/Δ) embryos. Ctnnb1Δ/Δ embryos were produced by intercrossing mice bearing Ctnnb1-deficient eggs and sperms. We found that Ctnnb1Δ/Δ embryos developed to the blastocyst stage; thereafter, they were resorbed, leaving empty decidual capsules. Moreover, leukemia inhibitory factor, a uterine factor essential for implantation, was undetectable in Ctnnb1Δ/Δ blastocysts. Furthermore, CDX2, a transcription factor that determines the fate of trophectoderm cells, was not observed in Ctnnb1Δ/Δ blastocysts. Intrauterine injection with uterine fluids (from control mice) and recombinant mouse leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1Δ/Δ blastocysts. These results suggest that embryonic CTNNB1 is required for the secretion of blastocyst-derived factor(s) that open the implantation window, indicating that the uterine response to implantation can be induced using supplemental materials. Therefore, our results may contribute to the discovery of a similar mechanism in humans, leading to a better understanding of the pathogenesis of repeated implantation failure.

Assisted reproductive technology in Japan: A summary report for 2020 by the ethics Committee of the Japan Society of obstetrics and gynecology.

Purpose: Since 1986, the Japan Society of Obstetrics and Gynecology assisted reproductive technology (ART) registry system has collected data on national ART use and outcomes trends in Japan. Herein, we describe the characteristics and outcomes of ART cycles registered during 2020 and compare the results with those from 2019. Methods and Results: In 2020, 621 ART facilities participated in the registration. The total number of registered cycles was 449 900, and there were 60 381 live births, which decreased from the previous year (1.79% and 0.36% decrease, respectively). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles increased in 2020, and the number of neonates born was 2282 for IVF-embryo transfer (ET) cycles and 2596 for ICSI cycles, which had decreased from the previous year. Frozen-thawed ET (FET) cycles had slightly increased from 2019 (0.04%). In 2020, 215 285 FET cycles were conducted, resulting in 76 196 pregnancies and 55 503 neonates. Single ET was performed in 81.6% of fresh transfers and 85.1% of frozen-thawed cycles, respectively, resulting in over 97% singleton pregnancies/livebirths rates. Conclusion: Despite the COVID-19 pandemic during 2020, the overall number of ART cycles and neonates born demonstrated only a slight decrease in 2020 compared with 2019.

Impact of the COVID-19 pandemic on surgery for benign diseases in gynecology: A nationwide survey by the Japan Society of Obstetrics and Gynecology.

AIM: This study aimed to clarify the impact of coronavirus disease 2019 on gynecology practice in Japan, in particular, on surgeries for benign gynecological diseases. METHODS: An online questionnaire was distributed to 966 facilities in Japan, including core facilities, facilities participating in perinatal and gynecologic oncology registries, and facilities certified for training by the Japanese Society of Obstetrics and Gynecology Endoscopy. The number of surgeries performed was compared between 2019 and 2020, when the novel coronavirus disease was prevalent. RESULTS: Five hundred and eighty (58.2%) facilities responded. The total number of surgeries decreased from 129 648 in 2019 to 118 565 in 2020, by 8.5%, for all surgical procedures. However, there was a clear increase in the number of robotic surgeries performed in 2020 compared to that in 2019 for all populations. The number of total hysterectomies decreased markedly from 15 385 in 2019 to 12 531 in 2020, a fall of 10.1%. CONCLUSIONS: The number of surgeries for benign gynecological diseases decreased by 8.5% in 2020 compared to that in 2019. This value is among the lowest in the world.

MicroRNAs secreted by human preimplantation embryos and IVF outcome.

OBJECTIVE: To generate an effective embryo prediction model and identify a non-invasive evaluation method by analyzing microRNAs (miRNAs) in embryo culture medium. DESIGN: Analysis of microRNA profiles from spent culture medium of blastocysts with good morphology that did or did not result in pregnancy. SETTING: Clinical and experimental research. PATIENTS: Sixty patients who underwent thawed embryo transfer of blastocysts after intracytoplasmic sperm injection. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The association of miRNA abundance levels secreted by blastocysts in culture medium and implantation success. RESULTS: Our RNA sequencing analysis found a total of 53 differentially expressed miRNAs in the culture media of pregnancy and non-pregnancy groups. Twenty-one miRNAs were analyzed for their potential to predict implantation success. Eight miRNAs (hsa-miR-191-5p, hsa-miR-320a, hsa-miR-92a-3p, hsa-miR-509-3p, hsa-miR-378a-3p, hsa-miR-28-3p, hsa-miR-512-5p, and hsa-miR-181a-5p) were further extracted from the results of a logistic regression analysis of qPCR Ct values. A prediction model for high-quality blastocysts was generated using the eight miRNAs, with an average accuracy of 0.82 by 5-fold cross validation. CONCLUSION: We isolated blastocyst miRNAs that may predict implantation success and created a model to predict viable embryos. Increasing the number of investigated cases and further studying the effect of each miRNA on embryonic development is needed to refine the miRNA-based predictive model.

The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan.

Purpose: In 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016-2019) and compared the results with our previous survey (2011-2015). The authors also surveyed reproductive specialists' awareness of the guidelines and implementation problems. Methods: The authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology. Results: The authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011-2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists' interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources. Conclusions: The practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.

Assisted reproductive technology in Japan: A summary report for 2019 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Purpose: The Japan Society of Obstetrics and Gynecology records online annual cycle-based information for assisted reproductive technology (ART). This report presents the characteristics and treatment outcomes of ART cycles registered during 2019. Methods: The Japanese ART registry includes cycle-specific information from 619 participating facilities, including treatment and pregnancy outcomes. Descriptive analyses were conducted for cycles registered during 2019. Results: In 2019, 458 101 treatment cycles and 60 598 neonates were reported, both of which increased from 2018. The number of fresh cycles, including in vitro fertilization and intracytoplasmic sperm injection, decreased, while frozen-thawed embryo transfer (ET) cycles increased. The mean maternal age was 37.9 years (standard deviation ± 4.7). Of 239 348 oocyte retrievals, 123 690 (51.7%) involved freeze-all-embryos cycles; fresh ET was performed in 41 831 cycles (a decreasing trend since 2015). In 2019, there were 211 597 frozen-thawed ET cycles, resulting in 74 882 pregnancies and 54 168 neonates born. Single ET was performed in 82.6% of fresh transfers and 85.1% of frozen-thawed cycles, with singleton live birth rates of 97.3% for both. Conclusions: The number of fresh cycles decreased but frozen cycles increased in 2019. Single ET was performed in >80% of cases, and the proportion of babies born from frozen-thawed ET increased.

Assisted reproductive technology in Japan: A summary report for 2018 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

PURPOSE: Since 2007, the Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle-based data for assisted reproductive technology (ART) in an online registry. Here, we present the characteristics and treatment outcomes of ART cycles registered during 2018. METHODS: The Japanese ART registry consists of cycle-specific information for all ART treatment cycles implemented at 621 participating facilities. We conducted descriptive analyses for such cycles registered for 2018. RESULTS: In total, 454 893 treatment cycles and 56 979 neonates were reported in 2018: both increased from 2017. The mean maternal age was 38.0 years (standard deviation ± 4.7). Of 247 402 oocyte retrievals, 118 378 (47.8%) involved freeze-all-embryos cycles; fresh embryo transfer (ET) was performed in 50 463 cycles: a decreasing trend since 2015. A total of 199 914 frozen-thawed ET cycles were reported, resulting in 69 357 pregnancies and 49 360 neonates born. Single ET (SET) was performed in 82.2% of fresh transfers and 83.4% of frozen-thawed cycles, with singleton pregnancy/live birth rates of 97.2%/97.2% and 97.0%/97.2%, respectively. CONCLUSIONS: Total ART cycles and subsequent live births increased in 2018. SET was performed in over 80% of cases, and the mode of ET has shifted continuously from using fresh embryos to frozen-thawed ones compared with previous years.

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.

Assisted reproductive technology in Japan: A summary report for 2017 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

PURPOSE: The Japan Society of Obstetrics and Gynecology (JSOG) has collected cycle-based assisted reproductive technology (ART) data in an online registry since 2007. Herein, we present the characteristics and treatment outcomes of ART cycles registered during 2017. METHODS: We collected cycle-specific information for all ART cycles implemented at participating facilities and performed descriptive analysis. RESULTS: In total, 448,210 treatment cycles and 56,617 neonates (1 in 16.7 neonates born in Japan) were reported in 2017, increased from 2016; the number of initiated fresh cycles decreased for the first time ever. The mean patient age was 38.0 years (standard deviation 4.6). A total 110,641 of 245,205 egg retrieval cycles (45.1%) were freeze-all cycles; fresh embryo transfer (ET) was performed in 55,720 cycles. A total 194,415 frozen-thawed ET cycles were reported, resulting in 66,881 pregnancies and 47,807 neonates born. Single ET (SET) was performed in 81.8% of fresh transfers and 83.4% of frozen cycles, with singleton pregnancy/live birth rates of 97.5%/97.3% and 96.7%/96.6%, respectively. CONCLUSIONS: Total ART cycles and subsequent live births increased continuously in 2017, whereas the number of initiated fresh cycles decreased. SET was performed in over 80% of cases, and ET shifted from using fresh embryos to frozen ones.

Impact of Oxidative Stress on Age-Associated Decline in Oocyte Developmental Competence.

Reproductive capacity in women starts to decline beyond their mid-30s and pregnancies in older women result in higher rates of miscarriage with aneuploidy. Age-related decline in fertility is strongly attributed to ovarian aging, diminished ovarian reserves, and decreased developmental competence of oocytes. In this review, we discuss the underlying mechanisms of age-related decline in oocyte quality, focusing on oxidative stress (OS) in oocytes. The primary cause is the accumulation of spontaneous damage to the mitochondria arising from increased reactive oxygen species (ROS) in oocytes, generated by the mitochondria themselves during daily biological metabolism. Mitochondrial dysfunction reduces ATP synthesis and influences the meiotic spindle assembly responsible for chromosomal segregation. Moreover, reproductively aged oocytes produce a decline in the fidelity of the protective mechanisms against ROS, namely the ROS-scavenging metabolism, repair of ROS-damaged DNA, and the proteasome and autophagy system for ROS-damaged proteins. Accordingly, increased ROS and increased vulnerability of oocytes to ROS lead to spindle instability, chromosomal abnormalities, telomere shortening, and reduced developmental competence of aged oocytes.

Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.

Zygotic genome activation (ZGA) begins after fertilization and is essential for establishing pluripotency and genome stability. However, it is unclear how ZGA genes prevent mitotic errors. Here we show that knockout of the ZGA gene Zscan5b, which encodes a SCAN domain with C2H2 zinc fingers, causes a high incidence of chromosomal abnormalities in embryonic stem cells (ESCs), and leads to the development of early-stage cancers. After irradiation, Zscan5b-deficient ESCs displayed significantly increased levels of γ-H2AX despite increased expression of the DNA repair genes Rad51l3 and Bard. Re-expression of Zscan5b reduced γ-H2AX content, implying a role for Zscan5b in DNA damage repair processes. A co-immunoprecipitation analysis showed that Zscan5b bound to the linker histone H1, suggesting that Zscan5b may protect chromosomal architecture. Our report demonstrates that the ZGA gene Zscan5b is involved in genomic integrity and acts to promote DNA damage repair and regulate chromatin dynamics during mitosis.

Membrane protein CD9 is repositioned and released to enhance uterine function.

Tetraspanin CD9 is essential for sperm-egg fusion and also contributes to uterine repair through microexosome formation. Microexosomes share CD9 with exosomes and are released from eggs and uterine epithelial cells. However, the mechanism for the formation of microexosomes remains unknown. To address this issue, we examined membrane localization and extracellular release of CD9 proteins using uterine epithelial cells and secretions in mice and humans. In mice, CD9 localized predominantly on the basal region of the plasma membrane and relocated to the apical region upon embryo implantation. Furthermore, extracellular CD9 proteins were detected in uterine secretions of mice and women undergoing infertility treatment, but were below detectable levels in supernatants of pluripotent stem cells. Ultrastructural analysis demonstrated that membrane projections were shortened and the number of mitochondria was reduced in uterine epithelial cells lacking Cd9 genes. Our results suggest that CD9 repositioning and release affect both membrane structures and mitochondrial state in the uterus, and contribute to female fertility.

Chemotactic behavior of egg mitochondria in response to sperm fusion in mice.

Mitochondria are the powerhouses of eukaryotic cells and their positioning contributes to fertilization and early developmental processes. We report that sperm fusion triggers Ca2+ oscillations and mitochondrial movement toward fused sperm (mitochondrial chemotaxis) in mouse eggs. Mitochondria functioned in Ca2+ storage and were colocalized with endoplasmic reticulum (ER) during Ca2+ oscillations. Mitochondria then moved toward the fused sperm. Sperm extracts lacking nuclei induced Ca2+ oscillations, but did not promote mitochondrial chemotaxis. Our results suggest that sperm fusion motivates Ca2+ oscillation-independent mitochondrial chemotaxis. This phenomenon indicates that egg mitochondria interact with sperm materials, presumably nuclear substances, and their network tethers egg and sperm nuclei at the early stage of zygote formation.

Degradation of phosphate polymer polyP enhances lactic fermentation in mice.

In bacteria, a polymer of inorganic phosphate (Pi) (inorganic polyphosphate; polyP) is enzymatically produced and consumed as an alternative phosphate donor for adenosine triphosphate (ATP) production to protect against nutrient starvation. In vertebrates, polyP has been dismissed as a "molecular fossil" due to the lack of any known physiological function. Here, we have explored its possible role by producing transgenic (TG) mice widely expressing Saccharomyces cerevisiae exopolyphosphatase 1 (ScPPX1), which catalyzes hydrolytic polyP degradation. TG mice were produced and displayed reduced mitochondrial respiration in muscles. In female TG mice, the blood concentration of lactic acid was enhanced, whereas ATP storage in liver and brain tissues was reduced significantly. Thus, we suggested that the elongation of polyP reduces the intracellular Pi concentration, suppresses anaerobic lactic acid production, and sustains mitochondrial respiration. Our results provide an insight into the physiological role of polyP in mammals, particularly in females.

Autophagy-disrupted LC3 abundance leads to death of supporting cells of human oocytes.

Autophagic recycling of cell parts is generally termed as the opposite of cell death. Here, we explored the relation between cell death and autophagy by examining granulosa cell layers that control oocyte quality, which is important for the success of fertilization. Granulosa cell layers were collected from infertile women and morphologically divided into four types, viz., mature (MCCs), immature (ICCs), and dysmature cumulus cells (DCCs), and mural granulosa cells (MGCs). Microtubule-associated protein light chain 3 (LC3), which is involved in autophagosome formation, was expressed excessively in DCCs and MGCs, and their chromosomal DNA was highly fragmented. However, autophagy initiation was limited to MGCs, as indicated by the expression of membrane-bound LC3-II and autophagy-related protein 7 (ATG7), an enzyme that converts LC3-I to LC3-II. Although pro-LC3 was accumulated, autophagy was disabled in DCCs, resulting in cell death. Our results suggest the possibility that autophagy-independent accumulation of pro-LC3 proteins leads to the death of human granulosa cells surrounding the oocytes and presumably reduces oocyte quality and female fertility.

Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after fusion to the egg.

The ubiquitin-proteasome system, which is initiated by a single ubiquitin-activating enzyme E1 (UBE1), is involved in male reproduction via spermatogenesis and function in mammals. Here we explored the influence of UBE1-specific inhibitor, 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (pyrazone-41 or PYR-41) in female reproduction. UBE-1 was detected by immunoblotting and immunocytochemistry in mouse eggs and was localized mainly under the egg plasma membrane. PYR-41 pretreatment suppresses the development of eggs into two-cell embryos. Specifically, pretreatment retarded sperm enlargement and meiotic chromosomal division after sperm-egg fusion. PYR-41 pretreatment disturbed ß-catenin, a well-known target protein for ubiquitination, localization under the egg plasma membrane and on spindle microtubules in wild-type eggs. Otherwise, PYR-41 treatment had no effect on the two-cell development of eggs lacking ß-catenin. Our results raise the possibility that inhibition of the ubiquitin-proteasome system suppresses sperm enlargement through impaired ß-catenin-mediated mechanism.

Clinical efficacy of a combination of Percoll continuous density gradient and swim-up techniques for semen processing in HIV-1 serodiscordant couples.

To evaluate the clinical efficacy of a procedure comprising a combination of Percoll continuous density gradient and modified swim-up techniques for the removal of human immunodeficiency virus type 1 (HIV-1) from the semen of HIV-1 infected males, a total of 129 couples with an HIV-1 positive male partner and an HIV-1 negative female partner (serodiscordant couples) who were treated at Keio University Hospital between January 2002 and April 2012 were examined. A total of 183 ejaculates from 129 HIV-1 infected males were processed. After swim-up, we successfully collected motile sperms at a recovery rate as high as 100.0% in cases of normozoospermia (126/126 ejaculates), oligozoospermia (6/6), and asthenozoospermia (36/36). The recovery rate of oligoasthenozoospermia was 86.7% (13/15). In processed semen only four ejaculates (4/181:2.2%) showed viral nucleotide sequences consistent with those in the blood of the infected males. After using these sperms, no horizontal infections of the female patients and no vertical infections of the newborns were observed. Furthermore, no obvious adverse effects were observed in the offspring. This protocol allowed us to collect HIV-1 negative motile sperms at a high rate, even in male factor cases. We concluded that our protocol is clinically effective both for decreasing HIV-1 infections and for yielding a healthy child.

Factors affecting pregnancy outcomes in young women treated with fertility-preserving therapy for well-differentiated endometrial cancer or atypical endometrial hyperplasia.

BACKGROUND: Patients hoping to preserve their fertility receive conservative treatment with high-dose medroxyprogesterone acetate (MPA) for well-differentiated endometrioid adenocarcinoma (EC) or atypical endometrial hyperplasia (AEH) . Such treatment generally involves frequent intrauterine operations, including dilation and curettage (D&C) and endometrial biopsy (EMB), which could result in endometritis, endometrial thinning, or intrauterine adhesion. In turn, any of these outcomes could adversely affect implantation and pregnancy development. The current study thus aimed to identify factors that might affect pregnancy following conservative treatment by MPA. METHODS: We compared a pregnancy group (45 patients) with a non-pregnancy group (53 patients) of MPA-treated patients to evaluate the factors affecting clinical pregnancy establishment. We undertook a multivariate logistic regression analysis based on factors shown by univariate analysis to be significantly different between the groups. Univariate analysis identified number of D&C, endometrial thickness, duration of MPA administration, age of pregnancy permission (the age at which a patient was first allowed to attempt pregnancy after disappearance of the lesion), period of disappearance of lesions, and recurrence as independent variables. RESULTS: The odds ratios (95 % confidence interval) of multivariate analysis for disease recurrence, endometrial thickness during ovulation, and age of pregnancy permission were 0.283 (0.102-0.785), 1.677 (1.251-2.248), and 0.889 (0.792-0.998), respectively. There was no significant difference in the other independent variables between groups. CONCLUSIONS: We identified three factors considered to affect pregnancy establishment following conservative treatment with MPA: recurrence, endometrial thickness during ovulation, and the age of the pregnancy permission. Introduction of infertility treatment including assisted reproductive technology (ART) soon after achieving tumor disappearance by MPA would therefore be beneficial for patients with disease recurrence, thin endometrium, or a higher age of pregnancy permission.