Mesenchymal stem cells for restoring endometrial function: An infertility perspective.

BACKGROUND: Mesenchymal stem cells (MSCs) can be derived from several tissues such as bone marrow, placenta, adipose tissue, or endometrial tissue. MSCs gain a lot of attention for cell-based therapy due to their characteristics including differentiation ability and immunomodulatory effect. Preclinical and clinical studies demonstrated that MSCs can be applied to treat female infertility by improving of the functions of ovary and uterus. This mini- review focuses on the current study of treatment of endometrial infertility by using MSCs. METHODS: The present study performed a literature review focusing on the effect of MSCs for treatment of women infertility caused by endometrial dysfunction. RESULTS: Bone marrow-, umbilical cord-, adipose-, amniotic-, and menstruation-derived MSCs enhance endometrial cell proliferation, injury repairs as well as reducing scar formation. The beneficial mechanism probably via immunomodulatory, cell differentiation, stimulates endometrial cell proliferation and down-regulation of fibrosis genes. The major advantage of using MSCs is to improve endometrial functions resulting in increased implantation and pregnancy. CONCLUSIONS: MSCs exhibit a potential for endometrial infertility treatment. Adipose- and menstruation-derived stem cells show advantages over other sources because the cells can be derived easily and do not causes graft rejection after autologous transplantation.

Primary omental pregnancy after in vitro fertilization complicated by hemoperitoneum-how to manage it laparoscopically.

OBJECTIVE: To report an uncommon case of primary OP treated laparoscopically. Ectopic pregnancy (EP) is the leading cause of maternal mortality during the first trimester and the incidence increases with assisted reproductive techniques, occurring in approximately 1.5%-2.1% of patients undergoing in vitro fertilization.1 Omental pregnancy (OP) is an extremely rare form of EP accounting for less than 1% of all EPs. OP can be classified as primary or secondary on the basis of Studdiford's criteria2. The preoperative diagnosis of OP is complex and usually occur in acute circumstances during a throughout intraoperative evaluation of the abdomen.3-5 A delayed diagnosis poses a serious threat to the survival of the patient; therefore, it is important to remark that EP can exist in unusual locations and prompt surgical intervention may be necessary. DESIGN: A step-by-step narrated video of a rare clinical case and description of the surgical procedure. SETTING: Tertiary Level Academic Hospital "IRCCS Azienda Ospedaliero - Universitaria di Bologna" Bologna, Italy. PATIENT: A 36-year-old woman was referred to our emergency room because of acute abdominal pain and nausea for 2 hours with no signs of hemodynamic instability. The patient also complained that poor vaginal bleeding appeared during the last 24 hours. The patient has undergone a cycle of in vitro fertilization with an elective single frozen embryo transfer of a blastocyst on day 5, 2 months before. She had no relevant clinical or surgical history. Diffuse abdominal tenderness and a painful uterus at mobilization were appreciated at clinical examination. A massive hemoperitoneum was diagnosed using transvaginal-transabdominal ultrasound, and no uterine or adnexal lesions were identified. The ß-human chronic gonadotropin level was 43.861 mIU/mL, and the hemoglobin value was 10.5 g/dL. INTERVENTIONS: On suspicion of a ruptured EP, after detailed counseling and the acquisition of informed consent, a laparoscopic exploration was planned. First, the hemoperitoneum was evacuated to allow visualization of the abdominal cavity. At pelvic inspection, no EP was found. Throughout the exploration of the abdominal cavity, a 4-cm bluish cystic mass of friable consistency was detected infiltrating the omentum and the mesentery. According to Studdiford's criteria, the diagnosis of a primary OP was established. A careful and complete excision of the ectopic implant was performed with an ultrasonic system and required a considerable hemostatic effort using bipolar energy, endoscopic clips, and mechanical compression. The postoperative course was uneventful. The ß-human chronic gonadotropin levels gradually decreased to negative values within 29 days after surgery. MAIN OUTCOME MEASURE(S): Omental ectopic pregnancy can be successfully managed with a laparoscopic approach even in an emergency setting. CONCLUSION: Omental pregnancy can easily be overlooked, even by skilled surgeons, during laparoscopic exploration. It is mandatory that all peritoneal surfaces and the omentum be carefully inspected during surgery in patients without other signs of pelvic EP.We confirm that the patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites, and other applicable sites.

Laparoscopic medulla-sparing ovarian tissue biopsy for cryopreservation: step-by-step surgical technique.

OBJECTIVE: To describe a laparoscopic technique for ovarian tissue biopsy (OTB) for fertility preservation. In the last years, the demand for fertility preservation has grown because of the increasing survival rates among patients with cancer and the rising awareness of the importance of quality of life after gonadotoxic therapy. Among fertility-sparing approaches, ovarian tissue cryopreservation is a valid strategy to preserve ovarian endocrine and reproductive function in prepubertal and postpubertal women who will undergo gonadotoxic cancer treatments. Currently, there is no universal consensus regarding ovarian tissue retrieval technique for fertility preservation. DESIGN: Step-by-step description of the surgical technique with narrated video footage. SETTING: Academic tertiary hospital. PATIENT(S): Patients with a high risk of premature ovarian insufficiency, usually due to gonadotoxic treatments, who undergo OTB for fertility preservation were included in the study. In this video, we present the clinical case of a 28-year-old patient affected by Hodgkin lymphoma who underwent laparoscopy for OTB before chemotherapy. INTERVENTION(S): After exposing the chosen ovary, an incision at the tubal pole of the ovary is made with scissors. Through section and dissection, a large cortical biopsy of the ovary is performed without removing and avoiding any damage to the medulla. At the end of the procedure, hemostasis was achieved with selective coagulation using bipolar coagulation. MAIN OUTCOME MEASURE(S): Step by step educational video. RESULT(S): The post-operative course was uneventful and the patient was discharge 24 hours after surgery. CONCLUSION(S): Standardization of a step-by-step laparoscopic technique can provide an effective method to optimize ovarian tissue removal while minimizing tissue injury. Medulla-sparing ovarian biopsy allows retrieval of only the cortical part of the ovary, maximizing the number of primordial follicles obtained without damaging the vascular supply of the ovary contained within the medulla. Primordial follicles are resistant to cryoinjury owing to their relatively inactive metabolism, and they are usually found at approximately 0.8 mm below the surface of the cortex. This technique could also reduce the back-table processing time of the ovarian tissue before cryopreservation. One disadvantage could be the difficulty of the technique compared to an oophorectomy because it requires a skilled surgeon that can easily find the cleavage plane between the medulla and the cortex, even in patients submitted to previous chemoradiotherapy or during gonadotropin-releasing hormone analogue therapy.

COVID-19 and human reproduction: A pandemic that packs a serious punch.

The COVID-19 pandemic has led to a worldwide health emergency that has impacted 188 countries at last count. The rapid community transmission and relatively high mortality rates with COVID-19 in modern times are relatively unique features of this flu pandemic and have resulted in an unparalleled global health crisis. SARS-CoV-2, being a respiratory virus, mainly affects the lungs, but is capable of infecting other vital organs, such as brain, heart and kidney. Emerging evidence suggests that the virus also targets male and female reproductive organs that express its main receptor ACE2, although it is as yet unclear if this has any implications for human fertility. Furthermore, professional bodies have recommended discontinuing fertility services during the pandemic such that reproductive services have also been affected. Although increased safety measures have helped to mitigate the propagation of COVID-19 in a number of countries, it seems that there is no predictable timeline to containment of the virus, a goal likely to remain elusive until an effective vaccine becomes available  and widely distributed across the globe. In parallel, research on reproduction has been postponed for obvious reasons, while diagnostic tests that detect the virus or antibodies against it are of vital importance to support public health policies, such as social distancing and our obligation to wear masks in public spaces. This review aims to provide an overview of critical research and ethics issues that have been continuously emerging in the field of reproductive medicine as the COVID-19 pandemic tragically unfolds.Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: Assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CCR9: C-C Motif Chemokine Receptor 9; CDC: Centers for Disease Control and Prevention; COVID-19: Coronavirus disease 2019; Ct: Cycle threshold; CXCR6: C-X-C Motif Chemokine Receptor 6; ELISA: enzyme-linked immunosorbent assay; ESHRE: European Society of Human Reproduction and Embryology; ET: Embryo transfer; FSH: Follicle Stimulating Hormone; FFPE: formalin fixed paraffin embedded; FYCO1: FYVE And Coiled-Coil Domain Autophagy Adaptor 1; IFFS: International Federation of Fertility Societies; IUI: Intrauterine insemination; IVF: In vitro fertilization; LH: Luteinizing Hormone; LZTFL1: Leucine Zipper Transcription Factor Like 1; MAR: medically assisted reproduction services; MERS: Middle East Respiratory syndrome; NGS: Next Generation Sequencing; ORF: Open Reading Frame; PPE: personal protective equipment; RE: RNA Element; REDa: RNA Element Discovery algorithm; RT-PCR: Reverse=trascriptase transcriptase-polymerase chain reaction; SARS: Severe acute respiratory syndrome; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SLC6A20: Solute Carrier Family 6 Member 20; SMS: Single Molecule Sequencing; T: Testosterone; TMPRSS2: transmembrane serine protease 2; WHO: World Health Organization; XCR1: X-C Motif Chemokine Receptor.