Advancing fertility preservation in prepubertal mice: Efficacy of ovarian tissue culture and in vitro growth in mature oocyte development.

AIM: This study aimed to evaluate the ovarian tissue culture and in vitro follicle growth as safer alternatives to cryopreservation for generating in vitro fertilization (IVF)-ready mature oocytes from prepubertal mice without the risk of cancer cell contamination. METHODS: Ovaries from prepubertal B6D2F1 mice were cultured in α-minimum essential medium supplemented with an estrogen receptor antagonist, ICI 182780. Culture duration was investigated to identify the optimal timeframe for follicle growth and oocyte maturation. Follicles were isolated mechanically or using 1 mg/mL collagenase and cultured in Matrigel matrix or polyvinylpyrrolidone. Oocyte development at metaphase II was induced by in vitro maturation, followed by IVF. RESULTS: The optimal culture duration was 2-4 days, and tissues cultured beyond this period showed significant follicular degeneration. ICI 182780 supplementation resulted in the recovery of 20.5 follicles per ovary compared with 9.5 follicles in non-supplemented cultures (p < 0.05). Of the 452 isolated follicles, 237 (52.4%) showed growth, 150 (33.2%) underwent germinal vesicle breakdown, and 18 (4.0%) reached metaphase II. However, none of the metaphase II oocytes were successfully fertilized after IVF. Matrigel demonstrated a significantly higher in vitro maturation rate compared with polyvinylpyrrolidone in a comparative analysis of culture matrices (p < 0.001). CONCLUSIONS: This study highlighted ovarian tissue culture and in vitro growth as effective strategies for producing mature oocytes from prepubertal mice. Further studies are required to overcome fertilization hurdles and understand the mechanisms that improve post-IVF embryo viability.

A case of non-Hodgkin lymphoma of the upper gingiva with minimal residual disease detected in cryopreserved ovarian tissue: A case report.

Recently, more than 200 live births following ovarian tissue cryopreservation (OTC) and transplantation in cancer survivors have been reported worldwide. However, cancer survivors with minimal residual disease (MRD) in cryopreserved ovarian tissue are at the risk of relapse through the graft. Here, we report a rare case of a 19-year-old female patient with non-Hodgkin lymphoma who had MRD in the ovary harvested for OTC. The patient was diagnosed with aggressive B-cell lymphoma after gingival biopsy. The 18F-fluoro-2-deoxy-D-glucose positron emission tomography scan performed before OTC showed no viable lesions in either ovary. However, on histological evaluation, we detected infiltration of lymphoma cells in the ovary. Informed consent about MRD is required even if there is no evidence of MRD in the ovary before OTC. Patients whose cryopreserved ovaries have MRD may require the development of alternative assisted reproductive technologies such as in vitro growth or artificial ovary.

Fertility-sparing management of stage IIIC serous borderline ovarian tumor: A case report of a 20-year follow-up.

Multimodal treatment, including assisted reproductive technology, is necessary in young patients with advanced borderline ovarian tumors. However, the details of long-term follow-up cases have not been reported. In this report, a 19-year-old patient presented with a stage IIIC serous borderline tumor. The patient underwent five fertility-sparing surgeries. The tumor did not respond to any of the three lines of chemotherapy administered. Serological and radiological responses were observed following hormonal treatment with leuprorelin, followed by a fourth surgery. Before the planned fifth surgery for complete resection of both adnexa, cryopreservation of the fertilized eggs was performed. At age 36, when the disease-free interval exceeded the previous one, we proposed embryo transfer; however, she declined fertility treatment. The patient had developed rheumatoid arthritis and childbirth not a priority. The patient had lived without any evidence of disease for 7 years following the last surgery and 20 years after the initial visit.

Primordial follicles remaining in young cancer survivors who received chemotherapy.

AIM: Ovarian tissue cryopreservation (OTC) is performed for fertility preservation in cancer patients undergoing chemotherapy. Although anti-Müllerian hormone is used as a marker for ovarian reserve, serum levels do not always correlate with the number of follicles. Additionally, the follicle development stage most affected by chemotherapy is unclear. We examined the association between serum anti-Müllerian hormone levels and the number of remaining primordial follicles after chemotherapy, as well as which follicle stage is most affected by chemotherapy before ovarian cryopreservation. METHODS: Thirty-three patients who underwent OTC were divided into the chemotherapy (n = 22) and non-chemotherapy (n = 11) groups; their ovarian tissues underwent histological examination. Pathological ovarian damage induced by chemotherapy was assessed. Ovarian volumes were estimated from weights. We compared the number of follicles at each developmental stage as a percentage of primordial follicles between the groups. The relationship between serum anti-Müllerian hormone level and primordial follicle density was analyzed. RESULTS: The chemotherapy group had a significantly lower serum anti-Müllerian hormone level, ovarian volume, and density of developing follicles than the non-chemotherapy group. Serum anti-Müllerian hormone levels correlated with primordial follicle density only in the non-chemotherapy group. The chemotherapy group had significantly lower numbers of primary and secondary follicles. CONCLUSIONS: Chemotherapy induces ovarian damage and follicle loss. However, serum anti-Müllerian hormone level does not always reflect the number of primordial follicles after chemotherapy, and chemotherapy more significantly affects primary and secondary follicles than primordial follicles. Many primordial follicles remain in the ovary after chemotherapy, supporting OTC for fertility preservation.

Sex difference in anti-sperm antibodies.

Background: Some diseases have sex differences. There have been no reports on the relationship between anti-sperm antibodies (ASA) and sex differences. Methods: ASA are detected by sperm-immobilization test using patients' sera in women. In men, the ASA testing is generally performed by direct-immunobead test. Main findings: Sperm-immobilizing antibodies in women inhibit sperm migration in their genital tract and exert inhibitory effects on fertilization. ASA bound to sperm surface in men also show inhibitory effect on sperm passage through cervical mucus. The fertilization rate of IVF significantly decreased when sperm were coated with higher numbers of ASA. For women with the antibodies, it is important to assess individual patients' SI50 titers. In patients with continuously high SI50 titers, pregnancy can be obtained only by IVF. For men with abnormal fertilizing ability by ASA, it is necessary to select intracytoplasmic sperm injection. Production of sperm-immobilizing antibodies is likely to occur in women with particular HLA after exposure to sperm. The risk factors for ASA production in men are still controversial. Conclusion: Attention to sex differences in specimens, test methods and the diagnosis of ASA should be paid. For patients with ASA, treatment strategies have been established by considering sex difference for each.

Evaluation of NKp46 expression and cytokine production of decidual NK cells in women with recurrent pregnancy loss.

Purpose: NKp46, a receptor on NK cells, is involved in cytotoxicity and cytokine production. The authors aimed to evaluate the effect of NKp46 on decidual NK (dNK) cells during pregnancy and whether it can be a marker for immunological abnormalities in women with recurrent pregnancy loss (RPL). Methods: Flow-cytometric analysis was made to assess NKp46 expression and intracellular cytokine production of dNK cells. The proportion of NKp46+ dNK cells was analyzed among RPL patients who aborted karyotypically normal pregnancies and those who either aborted karyotypically abnormal pregnancies or without genetic studies, and controls who were going through the induced abortion. Results: The %NKp46+ and %NKp46bright dNK cells were significantly lower in the RPL women who aborted karyotypically normal pregnancies than in the control group. The %NKp46bright dNK cells were significantly correlated with the NK1/NK2 ratio of dNK cells. The %NKp46+ dNK cell cutoff for RPL with immunological abnormalities was determined by the ROC curve analysis. In women with the low %NKp46+ dNK, NK1/NK2 ratios were significantly higher than those with the high. Conclusion: RPL patients with an immunological abnormality have decreased NKp46 expression and NK1 shift in dNK cells. NKp46 expression could be a marker for RPL of immunological abnormalities.

Clusters of smooth endoplasmic reticulum are absent in oocytes from unstimulated women.

RESEARCH QUESTION: What is the frequency of morphological dysmorphisms in immature human oocytes collected ex vivo from small antral follicles and matured in vitro? DESIGN: Human ovaries (n = 56) were excised for ovarian tissue cryopreservation (OTC). None of the patients had received exogenous gonadotrophins prior to the procedure. Immature oocytes released from small antral follicles were collected in connection with isolation of the cortex for OTC. The oocytes' maturation stage and the morphological characteristics of the cytoplasm, zona pellucida, perivitelline space and first polar body were assessed after in-vitro maturation (IVM). RESULTS: A total of 1649 immature oocytes were collected: 30% of oocytes matured to the metaphase II (MII) stage after IVM, while metaphase I (MI), germinal vesicle and degenerated oocytes accounted for 20%, 24% and 26%, respectively. The percentages of oocytes without any dysmorphisms were 53%, 92%, and 97% for the MII, MI and germinal vesicle stage oocytes, respectively. The most frequently observed dysmorphisms among the MII oocytes were first polar body fragmentation (22%), homogeneously distributed cytoplasmic granularity (16%) and an enlarged perivitelline space (14%). Interestingly, none of the oocytes at any stage had clusters of smooth endoplasmic reticulum (SER). CONCLUSIONS: Morphological dysmorphisms are present among in-vitro-matured oocytes at all maturation stages. The incidence of dysmorphisms increases as maturation progresses. The most frequent dysmorphism among MII oocytes after IVM was fragmentation of the first polar body. Clusters of SER were not observed in oocytes from unstimulated patients.

A threshold concentration of FSH is needed during IVM of ex vivo collected human oocytes.

PURPOSE: To investigate the effect of different FSH concentrations on human oocyte maturation in vitro and its impact on gene expression of key factors in the surrounding cumulus cells. METHODS: The study included 32 patients who underwent unilateral oophorectomy for ovarian tissue cryopreservation (OTC) (aged 28 years on average). Immature oocytes were collected from surplus medulla tissue. A total of 587 immature oocytes were divided into three categories according to the size of the cumulus mass: large (L-COCs), small (S-COCs), and naked oocytes (NOs), and submitted to 44-h IVM with one of the following concentrations of recombinant FSH: 0 IU/L, 20 IU/L, 40 IU/L, 70 IU/L, or 250 IU/L. After IVM, oocyte nuclear maturation stage and diameter were recorded. The relative gene expression of FSHR, LHCGR, and CYP19A1 in cumulus cells before (day 0; D0) and after IVM were evaluated. RESULTS: Addition of 70 or 250 IU/L FSH to the IVM medium improved oocyte nuclear maturation compared to 0, 20, and 40 IU/L FSH by upregulating LHCGR and downregulating FSHR in the cumulus cells. CONCLUSION: FSH improved oocyte nuclear maturation at concentrations above 70 IU/L suggesting a threshold for FSH during IVM of ex vivo collected human oocytes from small antral follicles. Moreover, current results for the first time highlight that FSH function in vitro is mediated via cumulus cells by downregulating FSHR and upregulating LHCGR, which was also observed when the immature oocytes progressed in meiosis from the GV to the MII stage.

Sperm immobilization test and quantitative sperm immobilization test using frozen-thawed sperm preparation applied with computer-aided sperm analysis.

PURPOSE: In a previous study, a new method was described using the sperm immobilization test (SIT) with computer-aided sperm analysis (CASA). However, obtaining high-quality sperm as needed was a known issue. Here, we compared the results of using frozen-thawed sperm and fresh sperm for the SIT using the CASA method. METHODS: For the frozen-thawed preparation, 500 µL of condensed semen and 500 µL of Sperm Freeze were mixed in a cryovial and cryopreserved in liquid nitrogen. Density gradient centrifugation was used for the collection of motile sperm in both the fresh and frozen-thawed sperm preparations. A total of 50 serum samples were prepared for both the fresh and frozen-thawed sperm with each sample tested containing 10 µL of serum, 1 µL of either fresh or frozen motile sperm suspension, and 2 µL of complement. Sperm motilities were measured using CASA after a 1-hour incubation period for both fresh and frozen-thawed sperm. RESULTS: Both fresh and frozen-thawed sperm reacted similarly when exposed to serum containing sperm-immobilizing antibodies asserting the use of frozen-thawed sperm for the diagnosis of immunological infertility. CONCLUSION: These results suggest the possibility of using cryopreserved sperm for the SIT when fresh sperm is unavailable.

Improving the maturation rate of human oocytes collected ex vivo during the cryopreservation of ovarian tissue.

PURPOSE: The aim of the present study was to improve the in vitro maturation (IVM) procedure using oocytes from surplus ovarian tissue after fertility preservation. METHODS: Twenty-five patients aged 17-37 years were included in the study. Maturation was compared between oocytes collected in HEPES-buffered medium or saline, and we determined whether transport on ice prior to oocyte collection affected maturation. Two different IVM media were used that were supplemented with and without recombinant human midkine. Mature oocytes were assessed for aneuploidy using next-generation sequencing (NGS). RESULTS: On average, 36 immature oocytes were collected from each patient (range 7-90, N = 895). Oocytes recovered from HEPES-buffered medium matured at a higher rate than oocytes recovered from saline (36% vs 26%, p < 0.01). Ovarian transportation on ice prior to the procedure negatively affected maturation compared with non-transported samples (42% vs 27%, p < 0.01). The addition of midkine improved maturation rate (34% vs 27%, p < 0.05). On average, 11 MII oocytes were obtained per patient (range 1-30). NGS of 53 MII oocytes and their first polar bodies indicated that 64% were euploid. CONCLUSIONS: The study demonstrated unexpectedly high number of immature oocytes collected from surplus ovarian tissue without any stimulation. The overall MII rate was one in three, resulting in a total number of MII oocytes that was similar to the number obtained after ovarian stimulation. If these MII oocytes prove suitable for IVF, they will provide a substantial improvement in fertility preservation for patients and advance IVM as an interesting platform for further improvements in assisted reproduction.

Time from referral to ovarian tissue cryopreservation in a cohort of Danish women.

INTRODUCTION: Young women with a cancer diagnosis often have very little time to decide whether or not to commence fertility-preserving strategies before initiating potentially sterilizing cancer treatment. Minimizing the interval from opting for fertility preservation to completion of the procedure will reduce the potential risk of delaying cancer treatment. In the current study, we have evaluated the period of time from referral to ovarian tissue cryopreservation (OTC) to actual freezing of the tissue in a cohort of Danish women. MATERIAL AND METHODS: The study population comprised 277 consecutive patients with both malignant and nonmalignant diseases referred for OTC from four centers in the Danish network. Statistical analysis was conducted to analyze the impact of age, diagnosis, and referring center on the time from OTC-referral to OTC. A literature search for "random start" protocols for controlled ovarian stimulation (COS) for fertility preservation in cancer patients was performed. RESULTS: The time from OTC-referral to OTC was significantly influenced by diagnosis, age, and referring center. Women with malignant diseases other than breast cancer, such as sarcomas, pelvic cancers, and hematological cancers, experienced a significantly shorter interval to OTC (5 days) than women with breast cancer (7 days) and nonmalignant diseases including systemic, ovarian, and hereditary conditions (13-17.5 days). Women over the age of 30 years experienced a significantly longer time to OTC (P < 0.03), and the diagnosis determined the length of the interval (P < 0.001). According to the literature, fertility preservation by oocyte vitrification requires 13-14 days, as the average time for 1 round of COS was 11 days and oocyte collection can be performed 2 days later. CONCLUSIONS: It is in the interest of both cancer patients and clinicians to perform fertility preservation as quickly and safely as possible. In a Danish setting, OTC provides a short interval of around 6 days from the patient choosing this option to completion of the procedure. This is considerably less time than what is needed to perform COS and oocyte vitrification, and therefore OTC might be considered the preferred choice of fertility preservation when urgency is needed.

Resuscitative hysterotomy in a patient with peripartum cardiomyopathy.

Resuscitative hysterotomy (RH) is a resuscitation technique, allowing the restoration of a pregnant patient's heartbeat. Here, we reported a case of RH performed in a patient with cardiac arrest as a complication of a peripartum cardiomyopathy. A 29-year-old woman with suspected hemolysis, elevated liver enzymes, low platelet syndrome was admitted to the hospital. Cardiopulmonary resuscitation and RH were initiated at 30 weeks of gestation. The infant was successfully delivered 2 min after the mother's cardiac arrest, weighting 1388 g. At the first minute, the Apgar score was 3 and the 5th minute was 6. After delivery, defibrillation was performed on the mother and restoration of spontaneous circulation was observed. However, she was hemodynamically unstable and approximately 2 months later she died. After cardiac arrest, it is possible that RH could improve the hemodynamic status. The opportunity of performing a RH is rare; however, it is necessary to be familiarized with the technique as a resuscitation method.

Association between spontaneous ovulation and serum anti-Müllerian hormone levels in a premature ovarian insufficiency patient after a multimodal treatment for breast cancer.

The high toxicity of chemotherapy can damage a patient's gonadal function, leading to premature ovarian insufficiency (POI). Here, we report the case of a patient suffering from POI after chemotherapy for breast cancer, who 3 years later ovulated spontaneously and became pregnant. The patient, a 31-year-old infertile women, nulligravida, was diagnosed with breast cancer. The Anti-Müllerian Hormone (AMH) level in her serum was 1.85 ng/mL before multimodal treatment for cancer. She later visited our hospital for amenorrhea and 2 years after cancer treatment, she was diagnosed with POI. Her AMH level at that point was less than 0.1 ng/mL. One year after the diagnosis of POI, the patient's AMH level increased slightly to 0.14 ng/mL and she ovulated spontaneously. The patient later became pregnant using Assisted Reproductive Technology on the fourth attempt.During the course of treatment for infertility at our hospital, the AMH levels in her serum changed along with the recovery of ovarian function. These findings suggest the possibility that ovulation and pregnancy could be predicted by the chronological changes of the AMH levels in the patient's serum.

Fertility preservation and pregnancy outcomes in adolescent and young adult male patients with cancer.

PURPOSE: Sperm cryopreservation is the gold standard for maintaining fertility in male survivors of cancer. In order to help increase the future success of fertility preservation in these patients, the present state of sperm cryopreservation was examined at the current institution and its challenges were discussed. METHODS: Between January, 2004 and February, 2017, 31 male patients with cancer were introduced to the center for fertility preservation. The ages and semen characteristics of these patients were examined and compared between those whose sperm were cryopreserved before (the pretreatment group) and after (the post-treatment group) cancer treatment. RESULTS: The mean sperm concentration of the pretreatment group was significantly higher than that of the post-treatment group. Normozoospermia was found in eight and three patients in the pretreatment and the post-treatment groups, respectively, albeit this difference was not significant. In contrast, the prevalence of azoospermia was higher in the post-treatment group (five patients) than in the pretreatment group (one patient). CONCLUSION: As many patients possibly suffer from infertility following chemotherapy, it is necessary to provide fertility preservation opportunities to young male patients with cancer prior to the commencement of cancer treatment.

Benefit of palliative chemotherapy and hospice enrollment in late-stage ovarian cancer patients.

AIM: The ideal timing for transition to best supportive care (BSC) for ovarian cancer patients is not clear. We retrospectively assessed the survival benefit of continuing chemotherapy and hospice enrollment in late-stage ovarian cancer patients. MATERIALS AND METHODS: Eligibility criteria included platinum and taxane treatment, clinical progression within 6 months of the last platinum dose, and progression during chemotherapy. RESULTS: Of the 55 eligible patients (median overall survival after first becoming refractory [1st Ref], 96 days), 22 received chemotherapy (Chemo group), two received radiation therapy, and 13 had medical contraindications for subsequent chemotherapy. The remaining 18 patients (BSC group) were compared with the Chemo group. The Chemo and BSC groups had similar background characteristics, except for the rate of consultation with a regional palliative care physician before or within 1 week of 1st Ref (9% vs 50%, respectively). In multivariate analysis, chemotherapy (hazard ratio 0.251, P = 0.005) and hospice enrollment (hazard ratio, 0.274, P = 0.023) were predictive factors of survival after 1st Ref. CONCLUSIONS: Chemotherapy after 1st Ref can be offered and hospice enrollment during the terminal stages is encouraged for recurrent ovarian cancer patients.

Update on the research on the antigens of anti-sperm antibodies over the last decade.

This review summarizes the advancements over a decade of research on antigens of anti-sperm antibodies (ASAs), which are key to male immune infertility. Despite the progress in assisted reproductive technologies, understanding the roles and mechanisms of ASAs and their antigens remains vital for immune infertility management. We conducted a comprehensive literature search on PubMed from January 2013 to December 2023 using the following keywords: "anti-sperm antibody," "sperm antigen," and "immune infertility." In this review, we focus on the discoveries in sperm antigen identification and characterization through proteomics, gene disruption technology, and immunoinformatics, along with the development of fertility biomarkers. Here, we discuss the clinical applications of improved ASA detection methods and the progress in the development of immunocontraceptive vaccines. The intersection of advanced diagnostic techniques and vaccine development represents a promising frontier in reproductive health. The findings also highlight the need for standardized ASA detection methods and a comprehensive molecular-level approach to understanding ASA-related infertility. These insights underscore the significance of ongoing reproductive immunology research in enhancing clinical fertility outcomes and contraceptive vaccine development.

Advancements in the detection and implications of sperm-immobilizing antibodies in female infertility.

This review highlights over five decades of research on sperm-immobilizing antibodies (SI-Abs), which are crucial for understanding female infertility due to their effects on sperm motility and fertilization. Since the 1960s, Isojima et al. have made significant strides, notably with the Sperm Immobilization Test (SIT), which revolutionized the quantification of SI-Abs and their roles in infertility. Drawing from a comprehensive PubMed search on "the sperm immobilization test" and "sperm immobilizing antibody," our review underscores the critical insights gained into SI-Abs' impact on reproductive functions. SI-Abs result from the body's response to sperm antigens, potentially leading to infertility by affecting post-intercourse sperm function. However, the presence of anti-sperm antibodies does not guarantee infertility, indicating a complex relationship between these antibodies and reproductive outcomes. Isojima et al.'s pioneering studies paved the way for SIT and sperm immobilization titer (SI50), tools that have clarified the link between SI-Abs and infertility, focusing on disrupted sperm mobility and fertilization as key infertility mechanisms. Clinically, interventions such as in-vitro fertilization (IVF), which bypasses or eliminates SI-Abs, have improved pregnancy rates, whereas Freund's complete adjuvant therapy has deepened our understanding of infertility mechanisms. The SI50 value is crucial for predicting fertility treatment success and guiding therapeutic decisions based on antibody levels. In summary, the evolution of SI-Abs research has provided new hope for addressing infertility, significantly enriching the field of reproductive immunology, and highlighting the need for ongoing investigation.

Anti-tubulin beta 4A (TBB4A) antibody immobilized sperm in a complement-dependent manner in humans.

Sperm-immobilizing antibodies (SI-Abs) are detected in the sera of 3 % of infertile women. SI-Abs are occasionally produced as allogeneic antibodies against sperm, causing immune infertility. SI-Abs inhibit the passage of sperm through the female reproductive tract. Research on anti-sperm antibodies (ASA) remains of great importance for population control. We aimed to identify the antigens recognized by SI-Abs and elucidate the pathogenesis of immune infertility. Twelve sperm-immobilization test (SIT)-positive and fourteen SIT-negative sera were analyzed by two-dimensional electrophoresis and western blotting. Antigenic materials were extracted from well-motile sperm prepared using 0.1 % sodium dodecyl sulfate. In total, 22 different spots were detected in the 12 positive sera. Among these, three positive serum samples showed two positive signals with similar migration patterns. The significant positive spots were Mr: 49 K, pI: 5.1 and Mr: 51 K, pI: 5.6. All these positive spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS); tubulin beta-4A (TBB4A) was identified from the spot Mr: 49 K, pI: 5.1. TBB4A is a major component of tubulin and constitutes the axoneme in the sperm tail and the centrosome in the sperm neck; it is generally located inside the cell. An authentic antibody against TBB4A showed a positive reaction in the sperm neck and tail regions in an immunofluorescence study. This antibody also inhibited sperm motility in a complement-dependent manner. Sperm membrane permeability reportedly changes during swimming and capacitation. We identified TBB4A as an antigenic molecule recognized by SI-Abs, which may be relevant to immunological contraception in the future.

Possible Role of 5-Hydroxytryptamine (5-HT) Receptor on Human Sperm Motility Regulation.

The purpose of this study is to examine whether 5-hydroxytryptamine (5-HT, also known as serotonin) regulates human sperm motility, focusing on 5-HT receptors. Immunofluorescent staining revealed the existence of seven types of 5-HT receptors with a heterogeneous pattern of reactive sites. In detail, 5-HT1B, 5-HT6, and 5-HT7 were detected in the post-acrosomal and mid-piece regions. The 5-HT2A and 5-HT5A receptors were mainly localized in the equatorial segment. 5-HT3A and 5-HT4 receptors were present in the neck and post-acrosomal regions. When examining the effects of 5-HT receptor antagonists on sperm motility, only the 5-HT2A receptor antagonist significantly reduced sperm motility. This suggests that the 5-HT2A receptor may have a regulatory function in sperm motility. Eventually, progressive motility should be attenuated to penetrate the oocyte for fertilization. The current study indicated heterogenous expression patterns and plausible functions of 5-HT receptors in human sperm.

Management of Hypervascular Retained Products of Conception With Massive Bleeding.

Retained products of conception (RPOC) could be a factor for massive postpartum hemorrhage; however, a management protocol is yet to be established. Performing a surgical intervention is controversial due to the potential for natural healing. Herein, we report the management of a hypervascular RPOC case with massive bleeding. Abortion was performed in a 40-year-old patient with gravida 2 and para 0, at 20 weeks and five days of gestation following the detection of Down's syndrome on prenatal screening. Post-delivery transvaginal ultrasonography identified an intrauterine mass measuring 4cm × 5cm × 5cm. The patient was then followed up in the outpatient department. One month after the abortion, the patient developed abnormal vaginal bleeding. Transvaginal ultrasonography revealed a hypervascular myometrial RPOC with turbulent flow. Although the bleeding stopped upon her admission to our hospital, the patient developed recurrent abnormal vaginal bleeding after nine days of hospitalization, which resulted in a hemoglobin level drop to 5.9 g/dL. CT and MRI scan findings raised the suspicion of hypervascular RPOC or uterine artery pseudoaneurysm. Uterine artery embolization was performed, leading to diminished vascularity in the RPOC, which was confirmed through color Doppler ultrasonography. The remnant placenta was successfully resected hysteroscopically, and a subsequent transvaginal ultrasonography showed a decrease in blood flow. In conclusion, hypervascular RPOC, previously reported as uterine artery pseudoaneurysms, should be considered when detecting hypervascular myometrial lesions in postpartum ultrasonography. Hypervascular RPOC with hemorrhage might benefit from hysteroscopic resection after achieving hemostasis with uterine artery embolization. This case report highlights the potential risks of awaiting spontaneous resolution in large RPOC and suggests that timely surgical intervention is both effective and essential.