Intrauterine administration of paternal and maternal peripheral blood mononuclear cells mix as solution for repeated implantation failure.

To date, implantation is the rate-limiting step for the success of in vitro fertilization (IVF) treatment. Accumulating evidence suggests that immune cells contribute to embryo implantation, and several therapeutic approaches have been proposed for the treatment of recurrent implantation failure (RIF). Endometrial immune modulation with autologous activated peripheral blood mononuclear cells (PBMCs) is one of the most widely used protocols. However, the effect of intrauterine insemination of mixed paternal and maternal-activated PBMCs has not yet been attempted and studied. The aim of our study is to test the effect of the addition of paternal lymphocytes on the implantation rate in RIF patients. Mononuclear cells were isolated from the peripheral blood of 98 RIF patients and cultured for 72 h before insemination into the endometrial cavity 48 h before embryo transfer. Our patients were divided into 4 groups according to the type and number of PBMCs inseminations. Our study shows that activated PBMCs promoted clinical pregnancy rates (CPR) in all groups. Moreover, we found that the groups injected with more than 2 million cells showed a better clinical outcome and, more interestingly, patients inseminated with both paternal and maternal activated PBMCs showed the highest CPR, reaching 47.2%, in addition to the highest implantation rate 31. 2% and the live birth rate 41.39%. Our work demonstrates the importance of administering a large number of activated PBMCs with the addition of paternal activated PBMCs to immunomodulate the endometrium for the success of in vitro fertilization in RIF patients.

The status of ART in the public health sector in Africa: a multi-country survey.

RESEARCH QUESTION: What is the current availability of treatment with assisted reproductive technology (ART) in the public sector in Africa, and what are the facilitators and barriers towards its provision? DESIGN: Cross-sectional quantitative and qualitative data were collected in two phases from February 2020 to October 2021. Key informants were identified from countries known to provide ART in Africa based on data from the African Network and Registry for Assisted Reproductive Technology and the 2019 Surveillance from the International Federation of Fertility Societies. Quantitative data were collected via a structured questionnaire (Phase 1); public centre-specific quantitative and qualitative data were then collected via a semi-structured questionnaire followed by a virtual interview (Phase 2). Data were analysed descriptively. RESULTS: Informants from 18 countries reported the existence of 185 ART centres in 16 countries. Twenty-four centres (13.0%) in 10 of 16 countries (62.5%) were public. The majority of public centres (20/22 [90.9%]) reporting on ART performed <500 ART cycles per annum. Although public institutions covered most of the cost for ART, copayments from patients were universally required. The number of ART cycles per annum was inversely correlated to the copayment. Lack of policy and legislation, high costs and bureaucratic obstacles were identified by participants as the leading challenges in the delivery of public service ART. CONCLUSION: Lack of public ART services leads to chronic and profound health inequities. Enablers of public service ART in the region are the same known to support ART services in general, namely policy and legislation, appropriate funding and good health service infrastructure. Addressing these requires the collated efforts of many stakeholders.

A View from the past into our collective future: the oncofertility consortium vision statement.

PURPOSE: Today, male and female adult and pediatric cancer patients, individuals transitioning between gender identities, and other individuals facing health extending but fertility limiting treatments can look forward to a fertile future. This is, in part, due to the work of members associated with the Oncofertility Consortium. METHODS: The Oncofertility Consortium is an international, interdisciplinary initiative originally designed to explore the urgent unmet need associated with the reproductive future of cancer survivors. As the strategies for fertility management were invented, developed or applied, the individuals for who the program offered hope, similarly expanded. As a community of practice, Consortium participants share information in an open and rapid manner to addresses the complex health care and quality-of-life issues of cancer, transgender and other patients. To ensure that the organization remains contemporary to the needs of the community, the field designed a fully inclusive mechanism for strategic planning and here present the findings of this process. RESULTS: This interprofessional network of medical specialists, scientists, and scholars in the law, medical ethics, religious studies and other disciplines associated with human interventions, explore the relationships between health, disease, survivorship, treatment, gender and reproductive longevity. CONCLUSION: The goals are to continually integrate the best science in the service of the needs of patients and build a community of care that is ready for the challenges of the field in the future.

Perurethral transvesical route for oocytes retrieval: an old technique for a new indication in oncofertility.

We aimed to evaluate the safety and efficiency of the peruretheral transvesical oocyte retrieval in oncofertility. We conducted a retrospective comparative study in our assisted reproductive technologies center. STUDY GROUP: 28 pubertal young women affected by malignancies, referred for fertility preservation and refusing transvaginal (TV) procedure. CONTROL GROUP: 28 infertile patients, aged less than 25 years, who have undergone in vitro fertilization with TV oocyte retrieval. The ovarian stimulation was significantly longer on the study group. There was no difference between the two groups regarding mean number of collected metaphase II oocytes. One patient of the study group had a transient dysuria. These preliminary data suggest that, in oncofertility, peruretheral transvesical oocyte retrieval is an alternative when the TV route is refused or not feasible.

[Diagnostic hysteroscopy before the first in vitro fertilization. For whom?]. / Hystéroscopie diagnostique avant la 1ère Fécondation In Vitro. Pour Qui ?

BACKGROUND: For some teams, hysteroscopy, should be performed before each IVF attempt to maximize the chances of implantation because of the high cost, the investment in time and the psychological impact of each IVF cycle, but answer to the question of the systematic practice of hysteroscopy prior to IVF is far from settled. AIM: Assess the benefits of conducting a routine hysteroscopy before the first IVF / ICSI and to identify subgroups in whom this examination provides a real benefit. METHODS: This is a comparative retrospective study about 334 patients, included in an IVF program with micro-injection, in the center of ART of Aziza Othmana hospital of Tunis, for a period of one year. The results of ICSI in patients with a first attempt at IVF / ICSI were compared according to the realization (HSC +) or not (HSC-) of a diagnostic hysteroscopy prior to the first IVF attempt. results : The implantation rate in our series was 21.62%. We got a pregnancy in 128 cases, that is a pregnancy rate per transfer of 38.32%. The rate of live births was 29.34%, including 94.89% deliveries to terms with living fetus. We found no significant difference between groups "HSC +" and "HSC -" in terms of pregnancy rates of biological or clinical pregnancy rate or in terms of live births. But, in patients aged 40 and over, we found improved results of IVF in a meaningful way in the group "+ HSC". CONCLUSION: Our study finds no benefit in terms of outcomes of IVF/ ICSI to the completion of hysteroscopy in a systematic way, despite a high incidence of abnormalities detected by intra-cavity examination. The benefit of routine hysteroscopy is significant only in women 40 and older.

[Cost of medical treatment with methotrexate for ectopic pregnancy. Study comparing medical treatment versus laparoscopy. Experience of Aziza Othmana Hospital]. / Coût du traitement médical par méthotrexate de la grossesse extra utérine. Etude comparative traitement médical versus traitement coeliochirurgical. Expérience de l'Hôpital Aziza Othmana.

BACKGROUND: The ectopic pregnancy can be treated surgically (conservative or radical) or medically. Currently, the choice between medical and surgical treatment is a critical issue. One of the parameters of this choice is the total cost of management. AIM: To compare the cost of the management of ectopic pregnancy by medical treatment (methotrexate, MTX) and coeliochirurgicaux. METHODS: This is a prospective, comparative, nonrandomized,unicentric study, on 39 patients who have ectopic pregnancies treated with MTX versus 16 patients treated by laparoscopic surgery with conservative treatment. This study was collected at the service of Obstetrics and Gynecology Reproductive Medicine Aziza Othmana Hospital (Tunis) for a period of two years. RESULTS: The average cost of hospital stay per patient was 549.38 dt for the MTX group against 268.39 dt for laparoscopic surgery group (p <0.001). There was no statistically significant difference between the two groups. In terms of overall absenteeism, there is no statistically significant difference (16.43 vs 17.5 days). CONCLUSION: The initial treatment with MTX costs more cost than the conservative laparoscopic treatment and this is mainly due to the long period of hospitalization.

Hypoxemia and if it is the liver? Hepatopulmonary syndrome : about a case.

The hepatopulmonary syndrome is defined as the triad of liver disease, pulmonary gas exchange abnormalities leading to arterial deoxygenation and widespread pulmonary vascular dilatation. It is one of the not infrequently cases of dyspnea within patients with liver disease. We report the case of a 32-year-old woman with cirrohsis and portal hypertention who presented with dyspnea worsning progressively. The blood gas revealed a deep hypoxemia with a PaO2 rate 42mmHg but clinically well tolerated. Pulmonary embolism and pneumonia were rapidly excluded by a CT pulmonary angiography. An echocadiography done in order to find any heart disease suspected a patent foramen ovale. A transthoracic contrast echocardiography showed an important pulmonary vascular dilatation.The association of cirrohsis, pulmonary vascular dilatation and hypoxemia made the diagnos of hepatopulmonary syndrome.

[Quality of life during menstruation in women with an inherited bleeding disorder: report of 31 cases]. / Qualité de vie pendant les menstruations chez les patientes portueses d'un troble héréditaire de l'hémostase: a propos de 31 patientes.

BACKGROUND: Menstruations, by their abundance and their duration, can be a source of impaired quality of life. Women with inherited bleeding disorders appear to be, specially at risk. AIM: Assess the impact of menstrual blood loss on the quality of life for women with inherited bleeding disorders. METHODS: 31 women with various inherited bleeding disorders were interviewed. They completed a quality of life questionnaire. RESULTS: Von Willebrand disease was the most frequent inherited bleeding disorder in our population (38.7%). 54.8% of patients had a menstrual period more than 6 days 61.3% of them consider their menstrual flow to be normal. The general condition apart of the menstrual period was considered medium to poor in 35.5% of patients. The average score assessing the impact of menstruation on daily life was of 5.00 ± 3.47. Only 19.35% of patients felt that dysmenorrhea significantly affect their quality of life. Impaired quality of life was seen in 64.5% of patients according to score Aand in 41.9% of them according to score B. During menstruation 22.6% of the patients didn't do to work or to school because of the menstrual flow. On the other hand, 48.4% of patients were hospitalized at least once for a heavy menstrual flow. CONCLUSION: The quality of life during menstruation, in women with an inherited bleeding disorder, according to the different scores appear altered. Although because of the small size of our study population, we could not prove correlation between the importance of menstrual blood loss and the impairment of quality of life.

[Delivery in twin pregnancies. The experience of the obstetrics department of Aziza Othmana's Hospital, about 117 cases]. / L'accouchement des grossesses gémellaires. Expérience de la maternité de l'Hôpital Aziza Othmana : A propos de 117 cas.

BACKGROUND: The conduct and delivery of twin pregnancies are interspersed with as well as maternal fetal and neonatal complications. The obstetrician is faced with the birth of 2 children often fragile and a uterus often exposed to dynamic dystocia. AIM: To study the maternal and newborn morbidity and mortality in twins, in order to clear the optimal route of delivery in such circumstances. METHODS: A retrospective study over a period of 3 years (1 January 2005 to December 31, 2007), about 117 twin pregnancies. Inclusion criteria were a term exceeding 28 weeks and fetuses alive. We analyzed maternal complications during and after delivery and neonatal complications. RESULTS: Maternal complications were significantly more frequent in case of caesarean section. The frequency of perinatal complications (Apgar score, respiratory distress, immediate neonatal resuscitation and neonatal intensive care unit transfer) in the first twin was not influenced by the route of delivery as opposed to the second twin which Apgar score's alters when vaginally. The newborns of low birth weight (<1,500 Kg) and those whose term was less than 32 weeks were more at risk of an Apgar score <7 (at 1 and 5 minutes), respiratory complications, need for immediate resuscitation and transfer to intensive care and that statistically significant both for the 1st and the 2nd twins. CONCLUSION: The twins pregnancies' morbidity appears to be more related to prematurity and intra uterine growth retardation) more than to the mode of delivery and hence the interest to detect and prevent its anomalies. It seems that vaginal delivery has a deleterious effect at least for the second twin but cesarean section doesn't seem to be the solution. Better learning techniques and obstetric maneuvers would reduce morbidity.

[Basal fsh level is only predictive of the quantitative aspect of the ovarian response]. / Le taux basal de FSH à j3 du cycle est un facteur prédictif de l'aspect quantitatif de la réponse ovarienne à la stimulation.

BACKGROUND: Determination FSH and LH at day 3 of the menstrual cycle predicts the response to stimulation. AIM: To evaluate the value of FSH and LH measurements compared with women's age in predicting qualitative and quantitative ovarian response to gonadotrophin stimulation. METHODS: 305 patients underwent at least one intra cytoplasmic sperm injection (ICSI) cycle. The levels of FSH and LH at day 3 were determined in an earlier cycle. A good quantitative ovarian response was defined as ³3 oocytes retrieved and 3 embryos obtained. A good qualitative ovarian response was defined as a percentage of mature oocytes ³75% and immature ones²15% of the total number of oocytes retrieved with at least one top quality embryo obtained. RESULTS: Receiver operating characteristic (ROC) curves were generated for FSH, LH and female age. FSH is better than female age in predicting the number of oocytes retrieved (respectively ROCAUC=0.77, p=10-3 versus ROCAUC=0.73, p=10-3) and the number of embryos obtained (ROCAUC=0.69, p=10-3 versus ROCAUC=0.66, p=10-3). LH is non predictive. None of the three tested parameters was predictive of the fertilization and pregnancy rates. An FSH cutoff was calculated and a value of 7.8mUI/ml is associated with a sensitivity of 73% and a specificity of 70% for the prediction of ovarian response to controlled stimulation. CONCLUSION: Basal FSH level predicts good quantitative rather than qualitative response. LH is non predictive. FSH and LH do not predict pregnancy rate. Patients having high FSH levels should not be excluded from IVF/ICSI treatment.

Genetic landscape of a large cohort of Primary Ovarian Insufficiency: New genes and pathways and implications for personalized medicine.

BACKGROUND: Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yielding infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology. METHODS: 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. FINDINGS: A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromosomal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link. INTERPRETATION: We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogenesis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility. FUNDING: Université Paris Saclay, Agence Nationale de Biomédecine.

[Clinicals and biological aspects of ICSI cycles on patients with polycystic ovary syndrome]. / Aspects cliniques et biologiques de l'ICSI chez les femmes porteuses du syndrome des ovaires Polykystiques.

AIM: To analyse clinical et biological pecularities of Polycystics Ovarian Syndrome (PCOS) patients enrolled on ICSI cycles and compare them to normo-ovulatory women. METHODS: 100 controlled ovarian stimulation cycles for ICSI in women with PCOS and 200 cycles in normo-ovulatory women. RESULTS: There was no significant difference in term of cancellation rate (5.5% in PCOS group vs 5%; NS). The mean number of follicles was higher in patients with PCOS (18.1 +/- 8.5 vs 9.4 +/- 5.5; p < 0.05). Oocyte mature rate and fertilization rate were higher in PCOS group (67% vs 52%; p < 0.05) (75% vs 63.7%; p < 0.05) respectively. Grade 1 embryo rate was significantly higher in PCOS group (69% vs 53%; p < 0.05). Implantation rate (16.6% vs 12.1%; NS) and clinical pregnancy rate per transfer (31.5% vs 22.2%; NS) did not differ statistically in the two groups. Miscarriage rate was higher in PCOS group but this did not reach the statistical significance (20% vs 7.1%; NS). 11 cases of Ovarian hyperstimulation syndrome occurred in PCOS group versus 4 on normo-ovulatory group. CONCLUSION: Use of ICSI as fertilization technique was correlated with good biologic parameters on PCOS patients with better fertilization rate and embryo quality and similar pregnancy rate comparing to normo-ovulatory women. However, it still be great concern about high risk of miscarriages and Hyperstimulation ovarian syndrome.

Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama.

PURPOSE: Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care. MATERIALS AND METHODS: To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed. RESULTS: Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs. CONCLUSION: Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.

Building Oncofertility Core Competency in Developing Countries: Experience From Egypt, Tunisia, Brazil, Peru, and Panama.

Purpose: Little is known about oncofertility practice in developing countries that usually suffer from a shortage of health services, especially those related to cancer care. Materials and Methods: To learn more about oncofertility practice in developing countries, we generated a survey to explore the barriers and opportunities associated with oncofertility practice in five developing countries from Africa and Latin America within our Oncofertility Consortium Global Partners Network. Responses from Egypt, Tunisia, Brazil, Peru, and Panama were collected, reviewed, and discussed. Results: Common barriers were identified by each country, including financial barriers (lack of insurance coverage and high out-of-pocket costs for patients), lack of awareness among providers and patients, cultural and religious constraints, and lack of funding to help to support oncofertility programs. Conclusion: Despite barriers to care, many opportunities exist to grow the field of oncofertility in these five developing countries. It is important to continue to engage stakeholders in developing countries and use powerful networks in the United States and other developed countries to aid in the acceptance of oncofertility on a global level.

Tunisian Recommendations for resumption of Reproductive Medicine activity in the Covid-19 pandemic.

The activity of the Reproductive Medicine poses a dilemma in this pandemic Covid-19. In fact, this is a theoretically non-emergency activity except for fertility preservation with oncological reasons. The majority of fertility societies in the world such as the American Society for Reproductive Medicine (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) recommended stopping the inclusion of new patients and continuing only the In Vitro Fertilization (IVF) cycles that have already been initiated by promoting Freeze-all as much as possible. Initilaly, the "Société Tunisienne de Gynécologie Obstétrique" (STGO) issued national recommendations that echo the international recommendations. These recommendations were followed by the majority of IVF center in Tunisia. However, a number of new data are prompting us to update these recommendations.

Survey of Third-Party Parenting Options Associated With Fertility Preservation Available to Patients With Cancer Around the Globe.

Purpose: In the accompanying article, "Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe," we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. Methods: We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed. Results: We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. Conclusion: Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients.

Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe.

Purpose: Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods: Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health-funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results: Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion: This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements.

[Epidemio-clinical features of genital tuberculosis among Tunisian women: a series of 47 cases]. / Caractéristiques épidémio-cliniques de la tuberculose génitale chez la femme tunisienne: une série de 47 cas.

This study aimed to identify the epidemio-clinic, diagnostic, therapeutic and evolutionary features of genital tuberculosis (GT) among Tunisian women. We conducted a retrospective, descriptive study in the Department of Infectious Diseases at the La Rabta Hospital, Tunisia, over a period of 15 and a half years (January 2000 - June 2014). All patients hospitalized for genital TB were included in the study. The study focused on 47 cases. The average age of patients was 42.2 years. Eighteen women were from rural areas. Tuberculous contact was found in five cases. In all cases, the onset was insidious. Twenty-three patients showed one or several signs of TB infection. Tuberculin intradermal reaction (IDR) test was performed in 35 women (74.8%), it was positive in 26 cases (74%). Thirty-nine patients (83%) had undergone radiological examination using abdomino-pelvis ultrasound and/or CT scan. Diagnostic coelioscopy was performed in 37 cases (75.5%). Anatomopathological examination helped to confirm the diagnosis of GT in 42 cases (89.3%), showing epithelioid and giant-cell granuloma. We identified 21 cases of isolated GT, the remaining 26 cases had peritoneal involvement. All patients received specific antibiotic therapy combining isoniazid, rifampicin, pyrazinamide and ethamubutol with an average treatment duration of 12 months. No patient received corticosteroids or secondary surgery. Patients' outcome was favorable in 39 cases, 8 patients were lost to follow-up. Genital tuberculosis is rare, representing only 0.5% of extra-pulmonary tuberculosis, but it accounts for a high prevalence of clinical polymorphism. Diagnostic confirmation is difficult and it is based on bacteriological and/or histological examinations. Diagnosis should be suspected in patients with chronic abdominopelvic symptoms, in women with infertility associated with suggestive epidemioclinical manifestations.