Medically assisted reproduction (MAR) with sperm donation: Comparison of the profiles and medical pathways of unmarried women and women in heterosexual couples.

RESEARCH QUESTION: The legislation allowing unmarried women to undergo medically assisted reproduction (MAR) with sperm donation was adopted in France on August 2, 2021. This major advancement, and its impact on French society, led us to a closer examination of the requests made by unmarried women and the outcomes of ART attempts. DESIGN: A retrospective single center cohort study was conducted in a fertility center in Paris, France. All unmarried women and women in heterosexual couple seeking for MAR using sperm donation between September 2021 and October 2022 were included. Medical and socio-demographic data, as well as details and outcomes of MAR attempts were analyzed until October 31, 2023. RESULTS: Two hundred seventy-two unmarried women and 76 women in heterosexual couple were included. Results were compared between the two groups. Unmarried women were significantly older, with a significant decrease in anti-Müllerian hormone (AMH) and antral follicle count (AFC). They also exhibited a higher prevalence of gynecological pathologies associated with infertility, such as endometriosis. Unmarried women were more likely to work in intermediate occupations, whereas women in heterosexual couple more often had employee status. Among unmarried women who had undergone at least one MAR attempt by October 31, 2023, significantly lower cumulative early and ongoing pregnancy rates were observed. CONCLUSIONS: Female age appears to play a major role in the likehood of pregnancy and live birth. It is therefore crucial to inform women initiating the process of MAR with sperm donation that success is not guaranteed.

[Fertility preservation for transmen]. / Place de la préservation de la fertilité dans le parcours des hommes transgenres.

The evolution of medical techniques as well as legislative changes currently allow to propose fertility preservation strategies in the context of transidentity. During "female to male" transition, androgen therapy has an impact on gonadal function since it usually induces a blockage of ovulation with amenorrhea. Although this effect is reversible when treatment is stopped, the possible long-term effects of testosterone treatment on future fertility or health of future children are poorly known. In addition, transitional surgeries definitely compromise fecundity when they include bilateral ovariectomy and/or hysterectomy. Yet, although long ignored or poorly expressed, the desire for parenthood is a reality in transgender men. Fertility preservation options in FtM transition rely on oocyte or ovarian tissue cryopreservation. The purpose of this review is to provide an overview of the literature regarding fertility preservation in transgender men. Although series remain limited, the increase in the number of recently published articles reflects the interest in improving the management of fertility issues in transgender men.

Different formulas, different thresholds and different performance-the prediction of macrosomia by ultrasound.

OBJECTIVE: The sonographic prediction of fetal macrosomia affects obstetrical decision regarding the timing and mode of delivery. We aimed to compare the accuracy of various formulas for prediction of macrosomia at different thresholds. STUDY DESIGN: This was a retrospective cohort study of singleton gestations at term, with fetal biometrical measurements taken up to 7 days prior to delivery (2007 to 2014). Sonographic estimated fetal weight was calculated using 20 previously published formulas. Macrosomia prediction was evaluated for every formula utilizing: (1) measures of accuracy (sensitivity, specificity and so on); (2) comparison of the systematic and random errors (SE and RE), and the proportion of estimates within 10% of actual birth weight for macrosomic and non-macrosomic neonates. Performance measurements were evaluated for different macrosomia thresholds: 4000, 4250 and 4500 g. Best performing formula for every threshold was defined as the one with the lowest Euclidean distance (=SQRT(SE2+RE2)). RESULTS: Out of 7977 women who met the inclusion criteria, 754 (9.4%) delivered a neonate weighing ⩾4000 g, 266 (3.3%) delivered a neonate weighing⩾4250 g and 75 (0.9%) delivered a neonate weighing⩾4500 g. Considerable variability was noted between the accuracy parameters of the different formulas, with Woo's formula integrating Abdominal circumference (AC) and femur length (FL) as the most sensitive formula with the highest negative predictive value for all thresholds and Woo's formula using AC, FL and biparietal diameter (BPD) as the most specific for all thresholds. The same formula also demonstrated the best overall accuracy. Regardless of threshold chosen, 80% or more of formulas demonstrated negative systematic error, meaning lower EFW than actual birthweight. As for the Euclidean distance, Hadlock's formula (AC, FL and BPD) ranked the highest for the 4000 and 4250 g thresholds, whereas Shepard's formula (AC and BPD) ranked the highest for the 4500 g threshold. CONCLUSION: Considerable variability exist between formulas for prediction of neonatal macrosomia. Formulas by Hadlock's and Shepard's utilizing AC, BPD±FL were most accurate for macrosomia prediction at 4000, 4250 and 4500 g thresholds, respectively.

Sonographic estimation of fetal head circumference: how accurate are we?

OBJECTIVES: To assess the accuracy of sonographic estimation of fetal head circumference (HC). METHODS: We compared sonographic estimations of fetal HC with actual measurements performed immediately after delivery using 3008 sonographic examinations performed within 3 days prior to delivery. The following measures of accuracy were calculated: correlation with actual HC, systematic error, random error, simple error, mean absolute percentage error and fraction of estimates within 5% of actual HC. Multivariate logistic regression analysis was used to identify factors affecting the accuracy of sonographic HC estimation. RESULTS: There was a high correlation between sonographic and postnatal measurements of HC (r = 0.845, P < 0.001). Overall, sonographic HC measurements consistently underestimated actual HC measured postnatally (mean simple error, - 13.6 mm; 95% CI, - 13.2 to - 13.9), and the difference increased with gestational age. A high cephalic index (> 0.81) (odds ratio (OR), 0.3; 95% CI, 0.2-0.4), HC > 90(th) centile (OR, 0.5; 95% CI, 0.3-0.6), delivery by vacuum extraction (OR, 0.6; 95% CI, 0.4-0.8), gestational week (OR, 0.7; 95% CI, 0.6-0.9) and male fetal gender (OR, 0.8; 95% CI, 0.6-0.9) were associated with decreased sonographic accuracy. At term, breech presentation at the time of sonographic examination was associated with a higher sonographic accuracy compared with vertex presentation (-12.0; 95% CI, - 10.5 to - 13.5 vs. - 13.9 mm; 95% CI, - 13.6 to - 14.3; P = 0.02). The random error was relatively constant, and was unaffected by any of the obstetric factors studied. CONCLUSION: Sonographic estimation of HC is associated with significant underestimation compared with the actual postnatal HC. This measurement error may have important clinical implications and should be taken into account in the interpretation of sonographically measured HC.

Prostaglandin E2 induction of labor for isolated oligohydramnios in women with unfavorable cervix at term.

OBJECTIVE: To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. METHODS: We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. RESULTS: Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75-6.68). No differences were found with other outcomes. CONCLUSION: Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.

Macrophage suspensions prepared from a blood unit for treatment of refractory human ulcers.

This paper presents an innovative method for the treatment of refractory wounds, starting with a blood unit, that is based on a biological approach. Local wound repair is one of the major unresolved clinical problems. Age, infection, clinical conditions such as diabetes mellitus, cardiac, renal, lung and liver failure, malnutrition and immunological deficiencies are among the reasons for wound repair delay or failure. Many chronic ulcers resist conventional treatment and do not heal for months and years, thus causing substantial morbidity and even mortality. The method for macrophage suspension treatment consists of introducing into the wound live cells that play a major role in the process of wound healing. The suspension is prepared from a blood unit of a healthy donor in a cost-effective, closed, sterile system. In the process of preparation, the macrophages are activated by hypo-osmotic shock to enhance their various functions in wound repair. The cells are applied to the wound either by local injection or by direct deposition into the wound. In most cases (90%), only one treatment is sufficient. Since 1995, macrophage suspensions have been used successfully in more than 1000 patients in several hospitals in Israel, without any side effects. Our results show that the use of a macrophage suspension is a safe and effective therapeutic strategy that shortens the healing period, reduces risk of complications and morbidity and improves the quality of life for long-suffering patients. This treatment requires no hospitalization and can be given on an ambulatory basis.

Activated macrophages for treating skin ulceration: gene expression in human monocytes after hypo-osmotic shock.

Macrophages play a major role in almost all stages of the complex process of wound healing. It has been previously shown that the incorporation of a hypo-osmotic shock step, in the process of monocyte-concentrate preparation from a blood unit, induces monocyte/macrophage activation. As the macrophages are produced using a unique, closed and sterile system, they are suitable for local application on ulcers in elderly and paraplegic patients. Enhanced phagocytosis by the activated cells, as well as increased secretion of cytokines such as IL-1, IL-6, were detected in a recent study which are in accord with the very encouraging clinical results. In the present study, we used DNA microarrays to analyse the differential gene expressions of the hypo-osmotic shock-activated monocytes/macrophages and compare them to non-treated cells. Of the genes that exhibited differences of expression in the activated cell population, 94% (68/72) displayed increased activity. The mRNA levels of 43/68 of these genes (63%) were found to be 1.5-fold or higher (1.5-7.98) in the activated macrophages cell population as compared to the non-treated cells. Only four genes were found to have lower mRNA levels in the activated cells, with ratios of expression of 0.62-0.8, which may suggest that the changes are insignificant. A significant number of the genes that showed increased levels of expression is known to be directly involved in macrophage function and wound healing. This may correlate with the increased secretion of different cytokines by the activated macrophages depicted previously. Other groups of genes expressed are known to be involved in important pathways such as neuronal growth and function, developmental defects and cancer. The hypo-osmotic shock induces a gene expression profile of cytokines and receptors in the activated cells. These may evoke potential abilities to produce a variety of protein products needed in the wound healing process and may bring to light possibilities for other therapeutic applications of these cells.

Activation of human monocytes/macrophages by hypo-osmotic shock.

Phagocytosis and secretion of interleukins and growth factors put the macrophage in the centre of the wound healing process. For the last four years over 400 human ulcers have been treated in elderly and paraplegic patients by local application of monocytes prepared from a blood unit, in a unique, closed, sterile system. The process of preparation includes a step of hypo-osmotic shock, which induces monocyte/macrophage activation. This is different from any other known method of activation. In the present study we evaluated the efficacy of the hypo-osmotic shock. We found enhanced levels of IL-1 (P = 0.004) and IL-6 (P = 0.001) in the incubation medium (100% autologous serum) of the activated cells, as compared with controls, prepared in the same system. The IL-1 reached a plateau after 6 and 12 h incubation at 37 degrees C, in both experimental and control incubation medium. The level of IL-6 was further elevated after 12 and 24 h incubation in experimental and control incubation mediums (P = 0.001). The phagocytosis of fluorescent beads was markedly enhanced after hypo-osmotic shock (P = 0.005). The osmotic shock induced macrophages were compared to those stimulated with LPS, and osmotic shock was proved to be at least as efficient method of stimulation as LPS.

Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation.

Viral infection has been shown to induce aplastic anemia, unidentified types of hepatitis being the most common cause for aplastic anemia-associated viral hepatitis. The survival rate for this group of patients after bone marrow transplantation with stem cells from an HLA-matched sibling is not well known. The aim of this study was to determine the prevalence of hepatitis G virus (HGV) and transfusion transmitted virus (TTV) infection in non-A, non-B, non-C hepatitis associated-aplastic anemia (HAAA) patients, and to define the role of bone marrow transplantation (BMT) as a therapeutic modality for this disease. Sixty-eight patients (43 males and 25 females) with aplastic anemia, underwent allogeneic BMT at the Hadassah University Hospital between 1981 and 1997. Onset of hepatitis was defined as jaundice and elevated alanine aminotransaminase (ALT) levels. Onset of aplastic anemia was defined as the first date on which varying degrees of pancytopenia occurred: hemoglobin level below 10 g/dl, WBC below 2 x 10(9)/l and low platelet count 10 x 10(10)/l. Serial serum samples from HAAA patients were assayed for virological and/or serological markers of hepatitis A, B, C, D, E, G viruses, TTV and parvovirus B19. Seventeen of the 68 patients with aplastic anemia (25%) suffered from hepatitis, 12 males and five females, ages 5 to 36 years. The mean interval between onset of hepatitis and first indication of aplastic anemia was 62 days (range 14-225 days). The development of aplastic anemia was unrelated to age, sex or severity of hepatitis. Ten of the 17 patients (59%) achieved complete ALT recovery prior to the diagnosis of aplastic anemia. Serum samples were available for 15 patients; none had evidence of acute or active hepatitis A, B, C, D, E, G and TTV virus infection at the time of diagnosis. Parvovirus B19 DNA sequences were not detectable in 10 of 12 tested cases; two positive results were detected in serum samples obtained after blood transfusion, making the analysis of these positive results difficult. All 17 patients underwent BMT. The mean post-BMT follow-up period was 38 months (range 1 day-123 months), five patients (30%) died 1 to 160 days post BMT, and 12 (70%) are alive 31 to 123 months after BMT. Relapsing hepatitis was not observed in any of the patients. In conclusion, HAAA is a disease of the young and the etiologic agent associated with HAAA remains unknown. HGV, TTV and parvovirus B19 sequences were not detected in any of the HAAA cases. The survival rate after BMT with stem cells from an HLA-matched sibling is similar to that for patients with non-hepatitis-associated aplastic anemia.

Maze learning impairment is associated with stress hemopoiesis induced by chronic treatment of aged rats with human recombinant erythropoietin.

Mean cell volume (MCV) of erythrocytes has been reported to increase with age in humans, and to be negatively correlated with memory performance in humans and rats. We evaluated hematological changes in 21-mo old male Fischer 344 rats undergoing a 3-mo twice weekly subcutaneous injection of human recombinant erythropoietin (EPO). A baseline hematocrit (HCT) was obtained initially and repeated at monthly intervals to determine the effectiveness of EPO treatment. At 24-mo of age and after 3 mo EPO treatment, the rats were tested for their ability to learn a 14-unit T maze. Following maze testing, blood was drawn for hematologic analyses, including HCT, MCV, maximum swollen cell volume (MCVS), mean cell transit time (MCTT), and the membrane shear modulus of elasticity (G), the latter a derived measure of the relative elasticity of the red cell membrane. After 1 mo EPO treatment, HCT significantly increased compared to saline-injected controls. After 2 mo treatment, HCT began to decline but remained elevated above baseline levels even after 3 mo treatment. After 3 mo EPO treatment, MCV was significantly lower in EPO-treated rats compared to controls. These changes imply altered hemopoiesis to produce cells which undergo shrinkage associated with accelerated cellular aging. The lower MCV would have predicted a shorter MCTT which instead was unchanged. This observation suggested the presence of an additional factor contributing to the MCTT. The G, which measures the membrane contribution to deformability, very significantly increased with EPO treatment. This finding indicates an increased contribution of membrane properties to the MCTT after EPO treatment, which cancels the expected decrease in MCTT for smaller cells. After 3 mo of EPO treatment, aged rats exhibited significantly impaired maze learning compared to controls. A relationship between, changes in erythrocyte membrane properties and impaired function was indicated by a significant correlation (r=0.67, p <0.04) between G and errors in the 14-unit T-maze. These findings suggest that stress-induced erythropoiesis produces accelerated aging in the red blood cell population that may have functional implications (i.e., impaired learning ability).

Treatment of human ulcers by application of macrophages prepared from a blood unit.

Decubital ulcers contribute to morbidity and mortality in elderly patients. Macrophages play a major role in the process of wound healing. We compared the efficacy of local treatment of decubital ulcers in elderly patients using macrophages prepared from a blood unit, vs. conventional treatments. Patients with decubital ulcers (n = 199) hospitalized during one year in a Geriatric Hospital in Israel, were included in the study. The ulcers of 72 patients (average age 82), who provided informed consent, by themselves or by family, were treated by local injection of macrophages prepared from a blood unit in a closed sterile system. The remaining 127 patients (average age 79) were treated conventionally and served as controls. No exclusion criteria were applied. Only a completely healed ulcer was considered a positive outcome of treatment. In the macrophage-treated group 27% (36 out of 131 ulcers) were healed compared to 6% (15 out of 248) in the control group (p < 0.001). There was also a significantly faster healing in the experimental group (p < 0.02). No side effects were noted. We conclude that Macrophages prepared from a blood unit, in cost-effective, closed, sterile system, are significantly more effective than conventional methods for the treatment of ulcers in elderly patients.

Chronic treatment with human recombinant erythropoietin increases hematocrit and improves water maze performance in mice.

Erythropoietin is a glycoprotein produced endogenously in the kidney, which stimulates red blood cell production. We evaluated the effects of chronic treatment with recombinant human erythropoietin (epoetin alfa: EPO) on the performance of 6-month-old male C57BL/6J mice in a spatial learning task, the Morris water maze. Mice were treated with either EPO (1.5 U injected SC every other day) or vehicle (PBS also injected SC every other day). Results indicated that the treatment had no effect on maze performance after 8 weeks, but after 19 weeks the EPO-treated mice showed better performance compared to controls as measured by mean distance (centimeters) to reach the goal platform. The improved performance in EPO-treated mice at 19 weeks was accompanied by an increased hematocrit. After 32 wk of EPO-treatment, the hematocrit returned to baseline levels even though the size and density of the red blood cells were increased.

Relationship of hematological variables to learning performance in aged Fischer-344 rats.

The relationship between hematological variables and the ability to perform behaviorally in two learning tests was evaluated in male F344 rats aged 22-24 months. Rats were screened for ability to meet criterion for learning one-way active avoidance in a straight runway task. Rats failing to meet criterion were given no further testing and were assigned to Group 1 (G1). Rats meeting criterion were tested in a 14-unit T-maze (2 days, 10 trials/day). Failure to negotiate the T-maze within 600 s on any three trials resulted in assignment to Group 2 (G2) with no further testing. Rats successfully completing both tasks constituted Group 3 (G3). Trunk blood was collected following behavioral testing and was assayed to determine red blood cell count (RBC), hematocrit (HCT), hemoglobin (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cell count (WBC), bands (BND), polymorphs (POLY), lymphocytes (LYM), monocytes (MON), and eosinophils (EOS). The combined G1/G2 group had significantly lower RBC, HCT, HGB, and EOS but significantly higher MCV and MCH than G3 rats. Correlation analysis revealed a positive relationship of group membership (i.e., learning test completion) to RBC, HCT, HGB, and EOS, but a negative correlation of group membership to MCH. No significant correlation emerged between any hematological characteristic and performance in either behavioral task. These results suggest that a simple blood test to determine HCT may be a useful screen for removal of moribund rats from aging studies attempting to control for effects of health on behavioral performance in rodent models.

Life span of erythrocytes in late pregnancy.

OBJECTIVE: Based on previous studies that demonstrated lighter and larger erythrocytes in late pregnancy, we hypothesized that the life span of erythrocytes in late pregnancy is shorter than in nonpregnant women. METHODS: We used the density distribution of cells to evaluate the age distribution of erythrocytes in pregnant versus nonpregnant women and rats. The life span of erythrocytes was compared between pregnant rats and nonpregnant syngeneic rats of the same age using 51Cr for labeling erythrocytes. RESULTS: Based on the density distribution of cells, a similar shift to lighter erythrocytes was found comparing pregnant to nonpregnant women and rats. The pregnant rat erythrocytes had a shorter life span by 9.2% (33.6 versus 36.9 days; P = .0010). CONCLUSIONS: The life span of erythrocytes in pregnant rats is shorter than in nonpregnant ones. A similar shift in the age distribution of pregnant rat and pregnant human erythrocytes is probably associated with a similar life span of pregnant rat and pregnant human erythrocytes. The shorter life span of erythrocytes in late pregnancy may be attributed to higher erythropoietin levels in pregnancy, which induce "emergency hematopoiesis" resulting in younger reticulocytes and macrocytic erythrocytes, which are known to have a shorter life span.

Memory performance of young and old subjects related to their erythrocyte characteristics.

Several papers reported in recent years on a change in the age population distribution of the circulating erythrocytes in old mice, rats, rabbits, and humans. The results indicate the presence of a chronologically younger cell population in old animals and humans. The cells are typically lower in density and larger. In some reports, the cells have higher levels of enzymatic activity. We wanted to know whether changes in the characteristics of the circulating erythrocytes in old people are related to the changes in cognitive performance often observed in the elderly. Twenty young (20-40) and 21 old (70-90) volunteers submitted to memory and blood tests. Density and size distribution, aspartate aminotransferase/glutamic oxalacetic transaminase (AST/GOT) activity, and the level of glycosylated hemoglobin (HbA1) of erythrocytes were determined. The Wechsler Memory Scale--Revised (Wechsler, 1987) was used to determine general memory and delayed recall scores for each subject. We have confirmed that old subjects have larger and less dense cells. Erythrocyte volume was the only blood parameter examined that revealed statistically significant correlations with memory performance. The old subjects with no age-related memory impairment had significantly smaller cells than the other old subjects.

The effect of selective desalivation on wound healing in mice.

The effectiveness of wound licking in the acceleration of wound healing was evaluated in selectively desalivated mice. Rate of healing of experimentally induced cutaneous wounds was evaluated macroscopically by photography at 0, 2, 4, and 6 days after wounding. Sialadenectomy of submandibular and sublingual glands significantly slowed down wound healing in animals caged together compared to sham-operated controls. Separate caging as compared to caging in groups slowed down healing in sham-operated animals at day 2 but not at day 4 and 6. No effect on the rate of healing in sialadenectomized mice was observed in separate caging compared to mice caged in groups. Ligation of the parotid duct had an insignificant effect. The rate of wound healing of sublingual sialadenectomized mice was slower than that of sham-operated controls, but not as slow as those of sublingual and submandibular sialadenectomized mice. The results suggest that the rate of healing of experimentally induced cutaneous wounds of mice is slowed down when licking is prevented by separate caging which confirms previous reports. Licking with submandibular saliva seems to be more effective than sublingual saliva. Parotid saliva or minor salivary glands secretions are the least effective.

Age population distribution of erythrocytes in young and old healthy donors.

Reports from several laboratories on a shorter life span of erythrocytes (E) in old animals and humans, induced the authors to search for a simple method for determining the younger age distribution of E in the blood of 20 old (over 70), as compared to 20 young (below 40), healthy donors. The following tests were performed: 1) Density Distribution of Cells (DDC), 2) Osmotic Fragility, 3) Agglutinability of E by Poly-L-lysine, 4) Analysis of Aspartate Amino Transferase (AST) activity, 5) Test for the presence of immunoglobulin on the surface of E (rosette formation on K562 cells); and 6) All the usual clinical and hematological tests were performed in order to avoid pathology. The most significant difference between the blood of the young and the old was found in the DDC. The shift of the cumulative curve indicated a younger population of cells in the blood of the elderly. The activity of AST was higher in the blood of the elderly, also indicating a younger cell population. The rosette formation was higher with the E from the blood of the elderly, indicating that the E, had more immunoglobulins on their surface than the E from the blood of the younger donors.