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.

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.

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.

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.

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.

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.

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.

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.

[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.

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.

Corrigendum to "Extensive Thrombosis of the Inferior Vena Cava and Left Renal Vein in a Neonate".

[This corrects the article DOI: 10.1155/2015/569797.].

Progesterone for Luteal Phase Support in In Vitro Fertilization: Comparison of Vaginal and Rectal Pessaries to Vaginal Capsules: A Randomized Controlled Study.

BACKGROUND: In IVF, Luteal phase support is usually performed using vaginal progesterone. A part of patients using this route reports being uncomfortable with this route. We tried to study whether the rectal route could be an effective alternative and associated with less discomfort. PATIENTS AND METHODS: A prospective randomized controlled study. All patient were eligible for IVF treatment for infertility. After oocyte pickup, 186 patients were allocated to one the following protocols for luteal phase support: (i) rectal pessaries group: natural progesterone pessaries administered rectally 200 mg three times a day, (ii) vaginal pessaries group: natural progesterone pessaries administered vaginally 200 mg three times a day), and (iii) vaginal capsules group: natural micronized progesterone capsules administered vaginally 200 mg three times a day. On the day of pregnancy test, patients were asked to fill in a questionnaire conducted by an investigator in order to assess the tolerability and side effects of the LPS treatment taken. The primary endpoint was the occurrence of perineal irritation. RESULTS: Fifty eight patients were assigned to the rectal pessaries group, 68 patients to the vaginal pessaries group, and 60 patients to the vaginal capsules group. All patients adhered to their allocated treatment. Implantation and clinical pregnancy rates per transfer did not differ between the three groups. Perineal irritation, which was our primary endpoint, was the same for all the three groups (respectively 1.7 % versus 5.9 % versus 11.7%). Regarding the other side effects, more patients experienced constipation and flatulence with the rectal route, whereas more patients reported vaginal discharge in the vaginal capsules group. CONCLUSION: Rectal administration for luteal phase support is effective and well accepted alternative to vaginal route.

Extensive Thrombosis of the Inferior Vena Cava and Left Renal Vein in a Neonate.

Antenatal renal vein thrombosis is a rarely described diagnostic finding, with variable consequences on kidney function. We present the case of an affected fetus, born at 35-week gestation, with intrauterine oligohydramnios and two small kidneys. A renal ultrasound carried out after birth confirmed the presence of prenatal abnormalities. Renal vein thrombosis was not diagnosed at the time. The baby died 20 days later of kidney failure, metabolic acidosis, and polypnea with severe hypotrophy. Autopsy revealed atrophied kidneys and adrenal glands. The vena cava had thrombosis occupying most of its length. The right renal vein was normal, while the left renal vein was threadlike and not permeable. Histologically, there was necrosis of the left adrenal gland with asymmetrical bilateral renal impairment and signs of ischemic and hemorrhagic lesions. A review of thrombophilia was carried out and a heterozygous mutation in Factor V was found in both the mother and the child.

Application of a hyaluronic acid gel after intrauterine surgery may improve spontaneous fertility: a randomized controlled trial in New Zealand White rabbits.

OBJECTIVE: Intrauterine adhesions (IUAs) are the most common complication after hysteroscopy in patients of reproductive age. Intra-abdominal anti-adhesion gel reduces the incidence of adhesions, but effects on fertility after uterine surgery are not known. The objective of our work was to evaluate the effect of intrauterine anti-adhesion gel on spontaneous fertility after repeated intrauterine surgery with induced experimental synechiae in the rabbit model. MATERIALS AND METHODS: Twenty New Zealand White rabbits underwent a double uterine curettage 10 days apart and were randomized into two groups. Each rabbit served as its own control: one uterine tube was the treatment group (A), the second uterine tube was the control group (B) to avoid bias through other causes of infertility. Group A received a post curettage intrauterine instillation of anti-adhesion gel whereas group B, the control group, underwent curettage without instillation of the gel. After a recovery period, the rabbits were mated. An abdominal ultrasound performed 21 days after mating allowed us to diagnose pregnancy and quantify the number of viable fetuses. RESULTS: There was a significant difference in total fetuses in favor of group A, with an average of 3.7 (range, 0-9) total fetuses per tube against 2.1 (0-7) in group B (p = .04). The number of viable fetuses shows a trend in favor of group A, with an average of 3.4 (0-7) viable fetuses per tube against 1.9 (0-6) viable fetuses per tube in group B (p = .05). CONCLUSION: The use of immediate postoperative anti-adhesion gel improved fertility in an animal model after intrauterine surgery likely to cause uterine synechiae. This experimental model will permit comparison of different anti-adhesion solutions, including assessment of their tolerance and potential mucosal toxicity on embryonic development.

Diagnosis and Management of Formerly Called "Dysfunctional Uterine Bleeding" According to PALM-COEIN FIGO Classification and the New Guidelines.

In 2011, the FIGO classification system (PALM-COEIN) was published to standardize terminology, diagnostic and investigations of causes of abnormal uterine bleeding (AUB). According to FIGO new classification, in the absence of structural etiology, the formerly called "dysfunctional uterine bleeding" should be avoided and clinicians should state if AUB are caused by coagulation disorders (AUB-C), ovulation disorder (AUB-O), or endometrial primary dysfunction (AUB-E). Since this publication, some societies have released or revised their guidelines for the diagnosis and the management of the formerly called "dysfunctional uterine bleeding" according new FIGO classification. In this review, we summarize the most relevant new guidelines for the diagnosis and the management of AUB-C, AUB-O, and AUB-E.

Seminal vesicle agenesis: An uncommon cause of azoospermia.

Seminal vesicle malformations are a rare cause of obstructive azoospermia, often associated with other internal genitalia and upper urinary tract birth defects. We report 5 new cases of seminal vesicle agenesis in men presenting with hypospermia and azoospermia. Imaging showed seminal vesicle unilateral agenesis in all patients. The remaining seminal vesicle was hypoplastic in 3 cases, dilated in 1 case and with abnormally thick content in another case. Vas deferens agenesis was observed unilaterally in 2 patients and bilaterally in 2 other patients. No renal malformations were detected. Genetic study showed in all cases a 46 XY karyotype without any microdeletions. A single heterozygous cystic fibrosis transmembrane regulator gene mutation was diagnosed in 1 man, but not found in his partner. Intracytoplasmic sperm injection using sperm from a testicular biopsy was performed in 3 couples, without success.

Chromosomal evaluation in a group of Tunisian patients with non-obstructive azoospermia and severe oligozoospermia attending a Tunisian cytogenetic department.

Male infertility is the cause in half of all childless partnerships. Numerous factors contribute to male infertility, including chromosomal aberrations and gene defects. Few data exist regarding the association of these chromosomal aberrations with male infertility in Arab and North African populations. We therefore aimed to evaluate the frequency of chromosomal aberrations in a sample of 476 infertile men with non-obstructive azoospermia (n=328) or severe oligozoospermia (n=148) referred for routine cytogenetic analysis to the department of cytogenetics of the Pasteur Institute of Tunis. The overall incidence of chromosomal abnormalities was about 10.9%. Out of the 52 patients with abnormal cytogenetic findings, sex chromosome abnormalities were observed in 42 (80.7%) including Klinefelter syndrome in 37 (71%). Structural chromosome abnormalities involving autosomes (19.2%) and sex chromosomes were detected in 11 infertile men. Abnormal findings were more prevalent in the azoospermia group (14.02%) than in the severe oligozoospermia group (4.05%). The high frequency of chromosomal alterations in our series highlights the need for efficient genetic testing in infertile men, as results may help to determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations.

[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.