Female cancer survivors: sexual function, psychological distress, and remaining fertility.

PURPOSE: Improved survivorship in cancer patients leads to new challenging issues including potential impairment of quality of life, sexual function, and fertility. The aim of this study was to assess sexual dysfunction (SD) and psychological distress in female cancer survivors who underwent fertility preservation in the past in comparison to reviewed healthy control data from other published studies. Additionally, our focus was on the difference in SD between women with current desire to get pregnant and already completed family planning. METHODS: In this prospective study, 53 female cancer survivors who underwent fertility preservation at time of cancer diagnosis between 2010 and 2020 were invited to a gynecological exam, laboratory assessment, and two questionnaires (Female Sexual Function Index (FSFI) and Hospital anxiety and depression scale (HADS)) in 2022. These scores were compared to results in the literature of healthy controls and depending on anti-Mullerian-hormone (AMH) levels, current desire to have a child, and age. RESULTS: After a mean follow-up time of 70 ± 50 months, SD was detected in 60.4% (n = 32) of the 53 included patients. Normal results regarding HADS-D/anxiety and HADS-D/depression were found in 88.7% and 94.3% of patients, respectively. At time of follow-up, 69.9% (n = 40) regained regular menstrual cycles, 52.6% (n = 20) < 40 years showed a diminished ovarian reserve with AMH levels < 1.1 ng/ml and 28.3% (n = 15) suffered from infertility. CONCLUSION: Female cancer survivors may be at risk for SD. Cancer patients should be informed about possible sexual dysfunction already at the start of cancer treatment and during follow-up. In addition, contraception needs to be addressed if regular cycles occur as more than two-thirds of the women regained regular menstrual cycles.

NK and T Cell Subtypes in the Endometrium of Patients with Recurrent Pregnancy Loss and Recurrent Implantation Failure: Implications for Pregnancy Success.

BACKGROUND: RPL and RIF are challenges in reproductive medicine. The immune system plays a pivotal role in endometrial receptivity, successful implantation, and pregnancy complications. Immunological changes have been associated with RPL and RIF. Understanding immune dysregulation especially in NK and T cell subtypes may lead to better diagnostic concepts and treatments. From July 2019 to August 2020 patients with RPL and RIF underwent a standardized diagnostic procedure including endometrial biopsies. Immune cell analysis was performed using flow cytometry. Patients were contacted in March 2023 and interviewed concerning their pregnancy outcomes following diagnostics. RESULTS: Out of 68 patients undergoing endometrial biopsies, 49 patients were finally included. Live birth rates were high with 72% in RPL and 86% in RIF. Immune cell analysis revealed that patients with RPL had more cytotoxic CD56dimCD16high cells, while RIF patients had more CD56+ uNK cells. RPL patients with pregnancy complications showed increased NKT cell percentages. CONCLUSION: Our findings suggest specific immune changes in RPL and RIF patients, offering potential therapeutic targets. Tailored immunotherapy based on endometrial immunophenotyping might be an option, but further research is needed.

Sexual function in male cancer survivors is not correlated to sperm quality.

PURPOSE: Both infertility and erectile dysfunction (ED) are known long-term consequences of cancer treatment in young male cancer survivors. In the present study, we aimed to assess whether sperm quality and sexual function in male cancer survivors are associated. METHODS: In this prospective study, n = 244 patients male cancer survivors who underwent sperm analysis and cryopreservation between 2008 and 2018 prior to the initiation of gonadotoxic treatment were invited. In total n = 50 had a follow-up sperm analysis and completed two questionnaires, the Aging Males' Symptom Scale (AMS) and the International Index of Erectile Function (IIEF-EF). Differences between the individual parameters were analyzed using the Wilcoxon or Mann Whitney test. RESULTS: Azoospermia was present in n = 16/50 (32.0%) patients at time of follow-up. ED occurred in n = 9/43 (20.9%) patients and was observed more frequently in patients with oligo- or azoospermia than in those with normospermia, even though this association was not statistically significant. Sperm parameters (total sperm count, sperm concentration, progressive motility) did not differ between time of cryopreservation and time of follow-up. Mean total, somatic, psychological, and sexual AMS score was 23.6, 9.9, 6.6, and 6.8, respectively. Mean total IIEF-EF score was 27.3, indicating mainly mild ED. CONCLUSIONS: More than one-third of cancer patients suffered from azoospermia, and ED was primarily present in this subgroup. We recommend implementing the screening of sexual dysfunction in the annual sperm testing that should be offered to all men after gonadotoxic treatment. Our study highlights the importance of counseling young cancer patients on both aspects-future infertility and sexual function-prior to treatment and at follow-up visits.

Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art.

Around 1-5% of all couples experience recurrent pregnancy loss (RPL). Established risk factors include anatomical, genetic, endocrine, and hemostatic alterations. With around 50% of idiopathic cases, immunological risk factors are getting into the scientific focus, however international guidelines hardly take them into account. Within this review, the current state of immunological risk factors in RPL in international guidelines of the European Society of Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine (ASRM), German/Austrian/Swiss Society of Obstetrics and Gynecology (DGGG/OEGGG/SGGG) and the Royal College of Obstetricians and Gynecologists (RCOG) are evaluated. Special attention was drawn to recommendations in the guidelines regarding diagnostic factors such as autoantibodies, natural killer cells, regulatory T cells, dendritic cells, plasma cells, and human leukocyte antigen system (HLA)-sharing as well as treatment options such as corticosteroids, intralipids, intravenous immunoglobulins, aspirin and heparin in RPL. Finally, the current state of the art focusing on both diagnostic and therapeutic options was summarized.

Different Background: Natural Killer Cell Profiles in Secondary versus Primary Recurrent Pregnancy Loss.

(1) Background: Prior studies suggested a significant impact of previous live births on peripheral natural killer cells (pNK) in patients with recurrent pregnancy loss (RPL). Patients with primary RPL (pRPL, no live birth) showed higher numbers of pNK than secondary RPL patients (sRPL, ≥ 1 live birth). (2) Methods: To further determine immunological differences between RPL patients and controls, we analysed pNK subpopulations and activation markers in pRPL (n = 47), sRPL (n = 24) and controls with previous live birth (sCtrl, n = 25) and nullipara (pCtrl, n = 60) within a prospective study. Percentages and numbers of CD56dimCD16bright cells, subpopulations and activation markers (CD57+, CD62L+, NKG2D+, NKp46+) were measured in non-pregnant RPL patients and n = 85 controls (n = 60 pCtrl, n = 25 sCtrl) in the mid-luteal phase by flow cytometry. (3) Results: Compared to sRPL patients, sCtrls showed higher CD56+ and CD56dimCD16bright numbers. Further, sRPL patients showed lower numbers of CD56dimCD16brightNKG2D+ and CD56dimCD16brightNKp46+ than sCtrls. (4) Conclusion: We suggest a chronic immune stimulation leading to a lower NK-cell count in sRPL patients with a lower NK cytotoxicity. This underlines the necessity to investigate pNK subpopulations as well as pRPL and sRPL separately to delineate the immune alterations in RPL.

What is new in 2017? Update on fertility preservation in cancer patients.

The prevention of fertility loss due to cancer treatment as well as non-malignant causes has been gaining importance over the last few decades. Clinically applied modalities for fertility preservation in cancer patients include cryopreservation of oocytes and embryos, the application of GnRH agonists, ovarian tissue banking, and cryopreservation of ejaculated or surgically extracted sperm. In addition, several new possibilities to restore fertility are currently being investigated, such as the establishment of in-vitro culture systems for gonadal tissue, the development of artificial gonads, and the application of germline stem cells. This review aims to provide an update on the methods currently applied in clinical practice for fertility preservation, as well as to summarize the progress made in the development of novel strategies for fertility preservation.

Follicular growth after xenotransplantation of cryopreserved/thawed human ovarian tissue in SCID mice: dynamics and molecular aspects.

PURPOSE: To study the influence of xenotransplantation on follicular recruitment and growth in cryopreserved/thawed human ovarian tissue. METHOD: Two 3-mm pieces of cryopreserved/thawed human ovarian tissue obtained from female cancer patients (n = 11) were xenotransplanted into a subcutaneous neck pouch of 6-week-old ovarectomized SCID mice (n = 33) for 4 (n = 18) and 12 (n = 15) weeks. RESULT: Thirty-two out of 33 mice survived the entire observation periods. Graft recovery rate was 95.58 % (65 of 68 grafts). The percentages of primordial follicles after 4 weeks (P < 0.001) and 12 weeks (P = 0.009) of grafting were significantly lower in comparison to pregraft controls. The percentage of secondary follicle was significantly higher after 4 weeks of grafting (P = 0.018) and after 12 weeks (P = 0.001) of grafting in comparison to pregraft controls. Ki67 immunohistochemistry showed that proliferative follicles were significantly higher after 4 and 12 weeks of grafting compared to pregraft controls (P < 0.001). All follicles analyzed by TUNEL staining appeared healthy after xenotransplantation. The expression level of PTEN was reduced by 2.47-fold after 4 weeks of xenotransplantation, and this result was significant when 2-ΔCt were analyzed (P = 0.042). CONCLUSION: The higher proportion of growing follicles compared to resting follicles observed after xenotransplantation is most likely due to downregulation of PTEN gene expression followed by acceleration of follicular recruitment.