Transplantation of Refrozen Ovarian Cortical Strips Retrieved from a Cryopreserved Whole Ovary: Proof of Feasibility.

We report successful clinical outcomes after transplantation of refrozen-rethawed cortical strips from a cryopreserved whole ovary in a patient diagnosed with stage IIIb rectal adenocarcinoma. Whole ovary cryopreservation was proposed as a fertility preservation strategy in 2006 prior to radiotherapy, chemotherapy and oncological surgery. To allow for minimal residual disease screening before ovarian reimplantation, the whole ovary was thawed and dissected into cortical strips. While awaiting the results, the majority of the cortical strips were refrozen. These refrozen-rethawed cortical strips were laparoscopically grafted to 2 sites: the previously irradiated pelvic cavity and the non-irradiated extrapelvic cavity. Ovarian function resumption was assessed by recovery of menses, hormone levels, ultrasound and oocyte pick-up following controlled ovarian stimulation (COS). Restoration of ovarian function occurred 6 months after reimplantation, with recovery of menses and estradiol secretion. A total of 12 cycles were followed by the IVF department. A second reimplantation was performed 1.5 years later, since the grafts were found to have stopped functioning for >3 consecutive months. Overall, 3 fertilizable oocytes were retrieved transabdominally from the extrapelvic graft following COS, yielding 2 embryos and culminating in one fresh embryo transfer, but no pregnancy. Concerning the reimplantation site, no ovarian activity was detected in the graft placed in the previously irradiated pelvic cavity. Indeed, only fibrotic-looking tissue was observed in the pelvic site at second laparoscopy 1.5 years later, while ovarian activity was noted in the extrapelvic graft, showing a large antral follicle. All in all, transplantation of refrozen-rethawed cortical strips from a cryopreserved whole ovary can lead to ovarian function resumption and embryo development if grafted to a non-irradiated field.

Experience With Medical Treatment of Cesarean Scar Ectopic Pregnancy (CSEP) With Local Ultrasound-Guided Injection of Methotrexate.

Objective: Ectopic pregnancy within Cesarean section scars is a rare condition. Late diagnosis carries significant risk of bleeding with poor prognosis for survival. There is no consensus on the management of this type of pregnancy. Historically, our facility offered an intra-muscular injection of methotrexate that resulted in a significant failure rate and later need for surgery. We hypothesized that injecting methotrexate directly into the gestational sac would improve the success rate of the treatment. Patients and Methods: This retrospective, uni-centric study examined nine patients aged between 33 and 42 years (mean age = 36.5 years) with Cesarean scar ectopic pregnancy (CSEP) between 2010 and 2018. CSEP was diagnosed by transvaginal ultrasound at a mean gestational age of 8w0/7. CSEP was treated under general anesthetic by ultrasound-guided methotrexate injection directly into the gestational sac. HCG levels and subsequent childbearing were monitored post-treatment. Results: Half of the patients were asymptomatic at the time of diagnosis. All patients tolerated treatment well and all ectopic pregnancies were successfully removed. HCG levels returned to negative within 3 months without additional medical or surgical intervention. The post-treatment pregnancy rate was 50%. Discussions/Conclusions: Our findings indicate that local ultrasound-guided injection of methotrexate into the gestational sac is a safe and effective therapeutic approach when performed by a trained team on a hemodynamically stable patient in the early stages of CSEP.

One-Step Autologous Minced Cartilage Procedure for the Treatment of Knee Joint Chondral and Osteochondral Lesions: A Series of 27 Patients With 2-Year Follow-up.

BACKGROUND: Chondral and osteochondral lesions are being detected with increasing frequency. For large-diameter lesions, cell-based treatment modalities are speculated to result in the best possible outcome. PURPOSE: To prospectively evaluate the 2-year clinical and radiological results after the treatment of chondral and osteochondral knee joint lesions by a single-step autologous minced cartilage procedure. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: From February 2015 to June 2016, a total of 27 consecutive patients suffering from chondral or osteochondral lesions of the knee joint were treated using a single-step autologous minced cartilage procedure. All patients underwent preoperative and postoperative magnetic resonance imaging for the collection of AMADEUS (Area Measurement and Depth and Underlying Structures) and MOCART (magnetic resonance observation of cartilage repair tissue) scores. Clinical analysis was conducted by a numeric analog scale (NAS) for pain and knee function before the intervention and at 12 and 24 months postoperatively. RESULTS: A total of 12 female and 15 male patients (mean age, 28.7 years) were evaluated for a mean of 28.2 ± 3.8 months. The mean cartilage defect size encountered intraoperatively was 3.1 ± 1.6 cm2. There was a significant decrease in pain from 7.2 ± 1.9 preoperatively to 1.8 ± 1.6 (P < .001) at 2-year follow-up. Knee function improved from a mean of 7.2 ± 2.0 preoperatively to 2.1 ± 2.3 (P < .001) at 2 years after surgery. The mean preoperative AMADEUS score was 57.4 ± 21.4. Postoperatively, the mean MOCART score was 40.6 ± 21.1 at 6-month follow-up. No correlation was observed between the clinical data and the MOCART or AMADEUS scores. CONCLUSION: Overall, the findings of this study demonstrated that patients undergoing a single-step autologous minced cartilage procedure had a satisfactory outcome at 2-year follow-up. As a result, the single-step autologous minced cartilage procedure does represent a possible alternative to standard autologous chondrocyte implantation. Longer follow-up and larger cohorts are required to define the benefits of this procedure.

Impact of luteal phase support with vaginal progesterone on the clinical pregnancy rate in intrauterine insemination cycles stimulated with gonadotropins: a randomized multicenter study.

OBJECTIVE: To evaluate the effect of luteal phase support (LPS) in intrauterine insemination (IUI) cycles stimulated with gonadotropins. DESIGN: Randomized multicenter trial. SETTING: Academic tertiary care centers and affiliated secondary care centers. PATIENT(S): Three hundred and ninety-three normo-ovulatory patients, <43 years, with body mass index ≤30 kg/m2, in their first IUI cycle, with at least one patent tube, a normal uterine cavity, and a male partner with total motile sperm count ≥5 million after capacitation. INTERVENTION(S): Gonadotropin stimulation, IUI, randomization to LPS using vaginal progesterone gel (n = 202) or no LPS (n = 191). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live-birth rate, miscarriage rate, and duration of the luteal phase. RESULT(S): The primary outcome, the clinical pregnancy rate, was not statistically different between the treatment group (16.8%) and the control group (11%) (relative risk [RR] 1.54; 95% confidence interval [CI], 0.89-2.67). Similarly, the secondary outcome, the live-birth rate, was 14.9% in the treatment group and 9.4% in the control group (RR 1.60; 95% CI, 0.89-2.87). The mean duration of the luteal phase was about 2 days longer in the treatment group (16.6 ± 2.2 days) compared with the control group (14.6 ± 2.5 days) (mean difference 2.07; 95% CI, 1.58-2.56). CONCLUSION(S): Although a trend toward a higher clinical pregnancy rate as well as live-birth rate was observed in the treatment group, the difference with the control group was not statistically significant. CLINICAL TRIAL REGISTRATION NUMBER: NCT01826747.

Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support-Results of a Prospective, Randomized, Comparative Study.

Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols.

Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus.

BACKGROUND: Conflicting results regarding changes in mucosal IgA production or in the proportions of IgA plasma cells in the small and large intestines during HIV-infection have been previously reported. Except in individuals repeatedly exposed to HIV-1 but yet remaining uninfected, HIV-specific IgAs are frequently absent in mucosal secretions from HIV-infected patients. However, little is known about the organization and functionality of mucosal B-cell follicles in acute HIV/SIV infection during which a T-dependent IgA response should have been initiated. In the present study, we evaluated changes in B-cell and T-cell subsets as well as the extent of apoptosis and class-specific plasma cells in Peyer's Patches, isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and APRIL were also determined. RESULTS: Plasma IgA level was reduced by 46% by 28 days post infection (dpi), and no IgA plasma cells were found within germinal centers of Peyer's Patches and isolated lymphoid follicles. This lack of a T-dependent IgA response occurs although germinal centers remained functional with no sign of follicular damage, while a prolonged survival of follicular CD4+ T-cells and normal generation of IgG plasma cells is observed. Whereas the average plasma BAFF level was increased by 4.5-fold and total plasma cells were 1.7 to 1.9-fold more numerous in the lamina propria, the relative proportion of IgA plasma cells in this effector site was reduced by 19% (duodemun) to 35% (ileum) at 28 dpi. CONCLUSION: Our data provide evidence that SIV is unable to initiate a T-dependent IgA response during the acute phase of infection and favors the production of IgG (ileum) or IgM (duodenum) plasma cells at the expense of IgA plasma cells. Therefore, an early and generalized default in IgA production takes place during the acute of phase of HIV/SIV infection, which might impair not only the virus-specific antibody response but also IgA responses to other pathogens and vaccines as well. Understanding the mechanisms that impair IgA production during acute HIV/SIV infection is crucial to improve virus-specific response in mucosa and control microbial translocation.

Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection.

BACKGROUND: Primary HIV-infected patients display severe and irreversible damage to different blood B-cell subsets which is not restored by highly efficient anti-retroviral therapy (HAART). Because longitudinal investigations of primary HIV-infection is limited by the availability of lymphoid organs, we studied the tissue-specific B-cell dysfunctions in acutely simian immunodeficiency virus (SIV) mac251-infected Cynomolgus macaques. METHODS AND FINDINGS: Experiments were performed on three groups of macaques infected for 14, 21 or 28 days and on three groups of animals treated with HAART for two-weeks either initiated at 4 h, 7 or 14 days post-infection (p.i.). We have simultaneously compared changes in B-cell phenotypes and functions and tissue organization of B-cell areas in various lymphoid organs. We showed that SIV induced a steady decline in SIgG-expressing memory (SIgD(-)CD27(+)) B-cells in spleen and lymph nodes during the first 4 weeks of infection, concomitant to selective homing/sequestration of B-cells to the small intestine and spleen. SIV non-specific Ig production was transiently increased before D14p.i., whereas SIV-specific Ig production was only detectable after D14p.i., coinciding with the presence of CD8(+) T-cells and IgG-expressing plasma cells within germinal centres. Transient B-cell apoptosis on D14p.i. and commitment to terminal differentiation contributed to memory B-cell loss. HAART abrogated B-cell apoptosis, homing to the small intestine and SIV-specific Ig production but had minimal effect on early Ig production, increased B-cell proportions in spleen and loss of memory B-cells. Therefore, virus-B-cell interactions and SIV-induced inflammatory cytokines may differently contribute to early B-cell dysfunction and impaired SIV/HIV-specific antibody response. CONCLUSIONS: These data establish tissue-specific impairments in B-cell trafficking and functions and a generalized and steady memory B-cell loss in secondary lymphoid organs. Characterization of underlying mechanisms would be helpful in designing new therapeutic strategies to dampen B-cell activation and increases HIV/SIV specific antibody response.