A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of "Oncofertility Around the Globe" to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.

Validation of routine analytical method for injectable cyclosporine preparation control using HPLC-FIA assay.

OBJECTIVE: The aim of this study is to validate a new HPLC-FIA method for routine analytical control of cyclosporine injectable preparations and to evaluate the routine analytical control with this technic. MATERIAL AND METHODS: Cyclosporine dosage was carried out by the HPLC-FIA method. The column was replaced by a PEEK (polyetheretherketone) loop tubing. The mobile phase consisted of ultrapure water. The injection volume was 1µL with a flow rate of 1mL/min. All determinations were performed at 35°C. The detection was carried out at 210nm. The accuracy profile method was used to validate the HPLC-FIA assay of cyclosporine. Routine control was applied for each cyclosporine preparation using the HPLC-FIA developed method. An acceptance limit of ±10% of the theoretical concentration has been set for the conformity of the preparation. RESULTS: The accuracy profile shows the validity of our method for the dosage of cyclosporine in the concentration range studied (0.5-2.5mg/mL) with good linearity (correlation coefficient>0.999), high precision (the relative standard deviation [RSD] values, for both repeatability and intermediate precision, were<3%) and acceptable trueness (the relative biases were found<2%). In our study, 220 injectable cyclosporine preparations were analyzed: 85% were compliant. All analyzes were conform after a second standardized homogenization of 10 shakes. CONCLUSIONS: The proposed HPLC-FIA method is a reliable, fast, simple, precise method that can be easily used for the routine quality control of cyclosporine injectable preparations.

Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic.

PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.

[Low circulating anti-Müllerian hormone and normal follicle stimulating hormone levels: which prognosis in an IVF program?]. / Pronostic en fécondation in vitro des patientes ayant une AMH basse et une FSH normale.

OBJECTIVE: To evaluate the results of controlled ovarian hyperstimulation (COH) for IVF in patients with low anti-Müllerian hormone (AMH) and normal basal follicle stimulating hormone (FSH) and Estradiol levels (≤50 pg/mL). PATIENTS AND METHODS: A retrospective cohort study including 704 patients for whom AMH and FSH levels (measured between days 3 and 5 of the menstrual cycle) were available, is performed in the IVF center at the Sèvres Hospital (France). Three groups are designed and analyzed: group 1 with AMH less or equal to 2 ng/mL and FSH less or equal to 10 mUI/mL (study group), Group 2 with AMH greater than 2 ng/mL and FSH less or equal to 10 mUI/mL (control group) and Group 3 with AMH less or equal to 2 ng/mL and FSH greater than 10 mUI/mL (group with decreased ovarian reserve). RESULTS: IVF outcome for patients from the study group is significantly worse than that of the second but not than that of the third group. In the first group, the number of retrieved oocytes, the number of total obtained embryos, the clinical pregnancy rate and the live birth rate are significantly lower than in the second group; moreover, there are more cancelled cycles because of poor response in the first group. There is no difference with the third group. DISCUSSION AND CONCLUSIONS: This study shows that women with a low baseline AMH have a similar response to COH to the poor responders patients with a decreased ovarian reserve revealed by an elevated FSH level. Thus, when a woman undergoing IVF cycle presents a low AMH, she might be considered as a poor responder patient regardless of the FSH level and, although the clinical pregnancy rate is not so disappointing (18%), the couple should be informed of a higher risk of cycle cancellation.

Cystic fibrosis transmembrane conductance regulator mutations and polymorphisms associated with congenital bilateral absence of vas deferens in a restricted group of patients from North Africa.

BACKGROUND: Congenital bilateral absence of vas deferens (CBAVD) is responsible for 2-6% of male infertility. It occurs in 95% of men with cystic fibrosis. This malformation is present in patients with a sterile obstructive azoospermia but without clinical evidence of cystic fibrosis. Molecular study of the cystic fibrosis transmembrane conductance regulator (CFTR) gene responsible for cystic fibrosis could show the relationship between this disease and bilateral absence of vas deferens. PATIENTS AND METHODS: The study involved 20 male patients aged between 28-40 years, referred with suspected cystic fibrosis and in whom bilateral absence of vas deferens was confirmed by cyto-biochemical analyses and urogenital ultrasound. Molecular study of the CFTR gene was based on several techniques: DHPLC, DGGE and direct sequencing. RESULTS: Thirteen patients had CFTR mutations: F508del, G542X, W1282X, E1104X, 711+1G → T, V201M (TG) m and IVS8-5T. These mutations were associated with polymorphisms: M470V and D1270N. Seven cases presented only polymorphisms. CONCLUSION: The different mutations found in this study were associated with polymorphisms which decrease the severity of the disease and delay its onset. Thus, bilateral agenesis of the vas deferens is classed as a form of cystic fibrosis with only genital expression.

[Congenital heart block associated with maternal anti SSA/SSB antibodies :a report of four cases]. / Bloc auriculoventriculaire congénital associé à des autoanticorps anti-SSA/SSB maternels: à propos de quatre observations.

Congenital heart block (CHB) associated with maternal anti-SSA/SSB antibodies: a report of four cases. CHB detected in utero is strongly associated with maternal antibodies to SSA (Ro) and SSB (La). Their pathogenic role in the development of CHB has been established in several studies. The mothers of affected infants frequently had autoimmune disease (systemic lupus erythematosus, Sjögren's syndrome) or were entirely asymptomatic. It is very difficult to identify pregnant asymptomatic mothers carrying anti-SSA/SSB antibodies. We report four cases of infants born to asymptomatic mothers with anti-SSA/SSB antibodies, three of them developed isolated congenital cardiac heart block and one with no evidence of CHB. All three CHB are detected during pregnancy between 16 and 24 weeks of gestation. All maternal sera contained antibodies to SSA alone or the both SSA and SSB. Three of four subsequent pregnancies were complicated by heart block. One child affected died in utero. While the two other newborns with CHB required pacemaker insertion during the first 3 months of life. Although the association of anti-SSA/SSB with CHB is widely accepted, the precise mechanism by which these antibodies cause cardiac conduction abnormalities remains to be defined. Antibodies to SSA/SSB have been proposed to be a serologic marker for neonatal lupus syndrome and CHB. Fetal and neonatal diseases are presumed to be due to the transplacental passage of these IgG autoantibodies from the mother into the fetal circulation. Since these antibodies may have a pathogenic role in CHB, screening of infants with isolated CHB or neonatal lupus and their mothers for the presence of anti-SSA and anti-SSB is strongly recommended.

[Anatomo-clinical characteristics of ovarian fibrothecal tumors. 19 cases over 12 years: 1981-1992[]. / Caractéristiques anatomo-cliniques des tumeurs fibrothécales de l'ovaire. A propos de dix-neuf cas en douze ans: 1981-1992.

The quasi-constantly benign nature of fibrithecomas of the ovary has been known for many years. However, there have been very few studies of their incidence and clinical characteristics. The aim of this study, based upon 19 cases of fibrothecal tumours of the ovary operated upon at the Rabta maternity unit during a 12 year period, is to give an idea as to epidemiological factors, diagnostic conditions and treatment methods used among the women studied.

[Norplant contraception at the Rabta Tunis maternity hospital]. / Contraception par Norplant à la maternité de la Rabta Tunis.

612 women had the benefit of contraceptive implants in the Maternity Hospital of La Rabta in Tunis over a period of 5 years (1988-1992). This study aimed at analysing the tolerance of this method by studying a group of 508 normal women and 104 women at risk (58 women were heart-diseased, 22 nursing, 13 diabetic, 11 hypertensive). The typical woman in this group is thirty years old, having 3 children, and weighing 61 kg. The implants were most of the cases withdrawn because of problems related to the menstrual cycle that were observed in 37% of the cases, equally distributed among both groups of the series. Contraceptive implants failed in 1.79% of the cases.

[Norplant contraception at the Rabta Tunis maternity hospital]. / Contraception par Norplant a la maternite de la Rabta Tunis.

PIP: During 1988-1992, physicians used two study protocols to follow 612 women who had accepted the subdermal contraceptive implant Norplant at the Rabta Maternity Hospital of Tunisia. They used WHO criteria to select 375 women aged 18-40 (i.e., healthy women with no contraindications). The remaining 237 women and their infants underwent regular clinical and paraclinical examinations. 58 of these women had heart disease. 13 had diabetes mellitus. 11 women had hypertension. 22 women were breast feeding. The women's mean age was 30. They weighed on average 61 kg. Mean family size was three. 35% and 21% of the women used oral contraceptives or IUDs, respectively, before accepting Norplant. 57% experienced menstrual disturbances after accepting Norplant. 162 women (26.5%) asked for Norplant to be removed. Menstrual disturbances were the reason for removal among 37% of them. This rate was the same for both groups. 1.79% of the women conceived during Norplant use. None of these women had an ectopic pregnancy, however. None of the infants being breast fed had any problems with growth. Norplant appeared to have no adverse effects on lactation. Side effects occurred at the same rate in the healthy women as the women at risk. These findings show that women at risk tolerated Norplant well.^ieng

[Pelvic hydatid cyst and pregnancy. Four cases]. / Kyste hydatique pelvien et grossesse. A propos de 4 cas.

The association of pelvic hydatid cyst with pregnancy is rare. We collected 4 cases between 1981-1990. Our incidence is of 1/30000 deliveries. The diagnosis was suggested in 3 cases by the patient's country of origin and previous history of extra-pelvic hydatid disease. It is confirmed by ultrasonography, which is still the first choice examination. During the 3 pregnancies managed to term, we did not find any modification in the cyst. One patient had vaginal delivery twice; however complications, sometimes fatal, are reported in the literature. The time for surgery and the mode of delivery are discussed because of the rarity of this association.

[Lipid evolution during normal pregnancy]. / Evolution des lipides au cours de la grossesse normale.

We analyzed the relationship between the evolution of pregnancy and the amplitude of the lipid disorders in order to evaluate their chronologic transformations. This research concerned 83 pregnancies aged between 19-40 years during the 3 periods of gestation and 31 healthy control women in the same range of age. Our results showed an increased triglyceride in the 2nd period and an earlier decrease of both, cholesterol, phospholipid and apolipoproteins. These parameters showed a progressive increase of their blood concentrations during the 2nd and the 3rd period of pregnancy, in an other hand we evidenced a good correlation between gestational aged and these variations i.e.: triglyceride and mother's weight; this phenomenon could suggest an eventual role of the nutrition and the hygienic habitude in the lipid metabolism. The correlation between our observed lipid disorders and the mother's age or the parity were not significant.

[Iron status and pregnancy in Tunisian women]. / Statut martial et grossesse en Tunisie.

PIP: The authors studied hematological and iron status in 83 pregnant, Tunisian women during each trimester of pregnancy, and compared them with a group of 31 control women of childbearing age. The incidence of anemia (hemoglobin 11 g/100 ml) was 2-3 times higher among the pregnant women that the controls. In the group of pregnant women, the proportion of women with iron deficiency (serum ferritin 12 mcg/1) gradually increased, from 65% in the 1st trimester to 83% in the 2nd, and 95% in the 3rd. Over 1/2 of the controls (52%) were also found to have iron deficiency. In view of the risks relating to anemia and the possible repercussions of iron deficiency on the maternal and fetal health, systematic iron supplementation is recommended during the 3rd trimester of pregnancy. (author's modified)^ieng