Subdermal Progestin Implant and an Oral Combined Hormonal Contraceptive in Youth with Type 1 Diabetes.

STUDY OBJECTIVE: To determine the metabolic effects of the subcutaneous etonogestrel implant compared with an oral contraceptive in adolescents and young adults (AYAs) with type 1 diabetes (T1D) on body weight, body composition, glucose, lipids, and C-reactive protein levels. METHODS: This was a non-randomized, interventional, prospective study. Thirty-nine AYAs with T1D participated; 20 used the implant (Implant-T1D), and 19 used an oral combined contraceptive (OC-T1D). Body composition, HbA1c, intermittent continuous glucose monitoring, lipids, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated. RESULTS: All participants were followed for at least 12 months, and 26 completed the 24-month follow-up. No women discontinued the intervention due to adverse effects. Body weight increased by 0.8 ± 3.5 and 1 ± 2.9 kg in the OC-T1D and the Implant-T1D group at 12 months and by 2.6 ± 3.9 and 3.3 ± 3.6 kg at 24 months, respectively. OC-T1D and Implant-T1D had similar HbA1c, mean interstitial glucose levels, and time in range throughout the study; no significant difference over time was observed. hsCRP levels increased in both groups and were associated with BMI and HbA1c (P < .001 for both variables). Women in the OC-T1D group had higher total cholesterol, HDL-C, and triglyceride levels compared with the Implant-T1D. CONCLUSION: Glucose levels were similar in youth using the subdermal progestin implant and an OC. However, both AYA groups showed increased BMI, fat mass, and subclinical inflammation. Changes in lipid levels were associated with the OC method. These data highlight the importance of weight gain prevention in young women with T1D using hormonal contraception.

Acceptability of the contraceptive Sayana® Press when injected every four months: Results from a twelve-month trial in Brazil, Chile and the Dominican Republic.

OBJECTIVE: We assessed the acceptability of subcutaneous depot-medroxyprogesterone acetate 104 mg (Sayana® Press) when injected every 4 months for 12 months. STUDY DESIGN: We assessed acceptability using questionnaires within a clinical trial to evaluate contraceptive effectiveness of Sayana® Press when the reinjection interval was extended from 3 to 4 months. We enrolled 750 women aged 18 to 35 years and at risk of pregnancy at 3 centers in Brazil, Chile, and the Dominican Republic who agreed to use Sayana® Press every 4 months for 12 months. Acceptability outcomes included responses to questions about perception of bleeding patterns and side effects, likes, and dislikes about the regimen. We descriptively compared outcomes across study centers and between those who completed the study and those who discontinued early. RESULTS: Across the 3 centers, participants differed in age, marital status, years of schooling, and race. At the final visit, 90% reported being satisfied with Sayana® Press and 75% reported preferring to use this contraceptive every 4 months. The most common reasons women liked using Sayana® Press were for its duration of effectiveness, followed by amenorrhea. The most common dislike, when a reason was identified, was its effect on uterine bleeding, including amenorrhea reported by some participants. We also observed center-level differences in the proportion of women who liked amenorrhea. CONCLUSIONS: Satisfaction with Sayana® Press injected every 4 months was high across the 3 demographically diverse Latin-American centers. However, participants had varied feelings towards contraceptive-induced amenorrhea. IMPLICATIONS: We found that Sayana® Press when injected every 4 months was highly acceptable among women in 3 Latin American settings despite differences in their feelings toward contraceptive-induced amenorrhea. Our results suggest that there will be interest in using this method every 4 months if introduced into these settings.

Contraceptive effectiveness, pharmacokinetics, and safety of Sayana® Press when injected every four months: a multicenter phase 3 trial.

BACKGROUND: Sayana Press® is a 3-monthly contraceptive injection approved by regulatory agencies in more than 40 countries worldwide. Existing effectiveness and pharmacokinetics (PK) data suggest that high contraceptive efficacy may be maintained if the reinjection interval of Sayana Press is extended from 3 to 4 months. METHODS: We conducted a phase 3 trial at three sites in the Dominican Republic, Brazil, and Chile from September 2017 through April 2020. We enrolled 750 women at risk of pregnancy who agreed to use Sayana Press off-label every 4 months (3 treatment cycles) for 12 months. The effectiveness cohort included 710 participants randomized equally to receive injections in the abdomen or thigh. Forty additional participants received injections in the back of the upper arm for comparative PK analyses. The primary outcome was pregnancy, defined by a positive urine pregnancy test confirmed by ultrasound and/or serum human chorionic gonadotropin. Secondary outcomes included PK, safety, and acceptability. Laboratory and trial Sponsor staff were blind to injection site. This study is registered with ClinicalTrials.gov, number NCT03154125. FINDINGS: There were no pregnancies during follow-up; the Pearl Index during 629.3 woman-years (WY) of follow-up in the primary effectiveness analysis was 0.00 (95% CI 0.00, 0.59). Pharmacokinetic profiles differed by injection site, with higher geometric mean (GM) medroxyprogesterone acetate concentrations for the abdomen than the thigh and arm. At month 8, significantly higher GM concentrations were observed in the abdomen and the thigh as compared to the arm, as well as at month 12 in the abdomen as compared to the arm. Injection site reactions were reported by 10.7% of participants. INTERPRETATION: Both pregnancy and PK results confirm that Sayana Press is a highly effective contraceptive method when administered every 4 months. These findings may inform modification of the dosing schedule, or duration of the grace period for reinjection, or both, to reduce overall drug exposure while maintaining contraceptive efficacy. FUNDING: This work is made possible by the generous support of the American people through the U.S. Agency for International Development (USAID), provided to FHI 360 through Cooperative Agreement AID-OAA-A-15-00,045, and a grant from the Gates Foundation. The contents are the responsibility of FHI 360 and do not necessarily reflect the views of USAID, the United States Government, or the Gates Foundation, nor does any mention of trade names, commercial products, or organizations imply endorsement by FHI 360, USAID, the United States Government, or the Gates Foundation.

Long-acting contraception in adolescents and young women with type 1 and type 2 diabetes.

Adolescent pregnancy is a major public health problem worldwide. Adolescents living with diabetes are not aware of the risks of unplanned pregnancy and the high rate of fetal and maternal complications when gestation occurs in women with significant hyperglycemia. These data highlight the significance of pregnancy prevention in young women with diabetes. Long-acting reversible contraceptives (LARCs), which include subdermal progestin implants and hormonal and nonhormonal intrauterine devices (IUDs), have been recommended by the American College of Obstetricians Gynecologists and the American Academy of Pediatrics as a first-line contraceptive option for adolescents and young women. This article reviews LARC options for adolescents and young women with type 1 (T1D) and type 2 (T2D) diabetes as well as the possible complications and side effects.

Androgens Profile in Blood Serum and Follicular Fluid of Women With Poor Ovarian Response During Controlled Ovarian Stimulation Reveals Differences Amongst POSEIDON Stratification Groups: A Pilot Study.

Patients with poor ovarian response (POR) to exogenous gonadotropins stimulation for assisted reproductive technology (ART) have decreased circulating androgens during spontaneous cycles. The Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) is a 4-tier stratification of women with POR to controlled ovarian stimulation (COH) based on age and biomarkers of ovarian reserve has been proposed to maximize the clinical management of this group for ART. The aim of the present study was to characterize the levels of androgens during COH in follicular fluid (FF) and serum in POSEIDON subgroups and compared them with women of normal ovarian response. Sixty nine consecutive patients undergoing ART were included and testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), estradiol, sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) were measured in serum and FF collected at the time of oocyte pick-up. The number of retrieved oocytes was registered for each patient for their allocation to the respective POSEIDON subgroup. The control group comprised 19 women and the POSEIDON group 1 (age < 35, normal ovarian reserve biomarkers) n = 14, group 2 (age ≥ 35, normal ovarian reserve biomarkers) n = 8, group 3 (age < 35, poor ovarian reserve biomarkers) n = 6 and group 4 (age ≥ 35, poor ovarian reserve biomarkers) n = 22. Serum levels of total testosterone, androstenedione and DHEA-S were not different in group 1 vs. control but significantly decreased in group 3 vs. control. DHEA-S in FF was also significantly decreased in group 3 vs. control. In addition, serum testosterone was decreased in groups 2 and 4 vs. control; and serum androstenedione and estradiol were reduced in group 4 vs. control. No differences were observed for estradiol, SHBG and IGF-1 in FF. Finally, a high correlation between serum and FF DHEA-S was observed when data from samples of all groups were pooled. Group 1 did not show hypoandrogenemia however group 3 had low levels of all measured androgens in serum and DHEA-S in FF. Such differences might help to better characterize and/or improve the clinical management of women with POR according to their respective POSEIDON stratification.

Ovarian Function in Adolescents Conceived Using Assisted Reproductive Technologies.

STUDY OBJECTIVE: To compare ovarian function between adolescents conceived using assisted reproductive technology (AcART) and adolescents who were conceived spontaneously (AcSP). DESIGN: Multicenter study of ovarian function in AcART because of male or tubal infertility. SETTING: University Hospital. PARTICIPANTS: We evaluated 22 AcART and 53 AcSP at 1-2 years after menarche. The participants were born at term (≥37 weeks of gestation) with normal birth weights (≥2500 g) from singleton pregnancies. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Differences in ovulation, reproductive hormones, and ovarian morphology. RESULTS: AcART had an older age of menarche than that of AcSP, even after adjusting for maternal age at menarche, gestational age, and birth weight (P = .027). AcART had lower incidence of ovulation (P = .021) and higher luteinizing hormone serum levels (P = .01) than those of AcSP. The incidence of oligomenorrhea and the cycle length were similar between AcART and AcSP. AcART had levels of anti-Müllerian hormone, inhibin B, follicle-stimulating hormone, estradiol, and androgens similar to those of AcSP. The ovarian morphology, ovarian volume, and follicle counts were similar in both groups. CONCLUSION: AcART had later menarche, lower ovulation rates, and higher luteinizing hormone levels than those of AcSP. Future studies should investigate whether these findings are indicative of a risk of ovarian dysfunction later in life for AcART.

Anti-Müllerian hormone in type 2 and gestational diabetes during the second half of pregnancy: relationship with sexual steroid levels and metabolic parameters.

Hyperandrogenemia and hyperinsulinemia are observed in women with diabetes during pregnancy. The effect of diabetes on anti-Müllerian hormone (AMH) levels during pregnancy is unclear. The aim of this study was to determine the AMH levels in women with type 2 diabetes (T2D) and gestational diabetes (GD) compared to healthy (C) pregnant women during the second half of gestation. A prospective study of 69 pregnant women with T2D (N: 21), GD (N: 24) and C (N: 24) were followed up during the second half of pregnancy. Clinical assessments and blood samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of gestation. AMH, sexual steroids, insulin, homeostatic model assessment of insulin resistance, HbA1c levels were measured. AMH levels were similar between T2D, GD and C (p = .07). A decline of AMH levels during the second half of gestation was observed in the three groups (p < .0001). AMH levels were negatively associated with age (p < .001). A positive association between AMH and testosterone (p < .05) was found in all groups. A progressive decline of AMH levels is observed in diabetic and healthy women during the second half of pregnancy. Testosterone levels are an independent factor that influences AMH levels during pregnancy. However, AMH levels are not affected by the presence of diabetes during gestation.

Pregestational type 2 diabetes and gestational diabetes exhibit different sexual steroid profiles during pregnancy.

Higher androgen levels are observed in non-pregnant women with diabetes. Whether this hormonal profile is found during pregnancy is unknown. The aim of this study was to determine the sexual steroids levels in pregnant women with pregestational type 2 (T2D) and gestational diabetes (GD) compared to healthy control (C) pregnant women during the second half of pregnancy. A prospective study of 69 pregnant women with T2D (n = 21), GD (n = 24) and control (C, n = 24) was followed up during the second half of gestation. Clinical assessments and blood samples were collected at 26.7 (25-27.8); 34 (32-34.9) and 37.5 (37-40) weeks of gestation. Androgens, sex hormone-binding globulin (SHBG), estrogens, estradiol/testosterone (E/T) ratio, insulin, glucose, HOMA-IR, were measured. Testosterone, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) levels were higher in T2D compared with C at each sampling point during pregnancy, even after adjusting for BMI and age. Estrogens levels and estradiol/testosterone ratio were lower in T2D and GD compared with C. Hyperandrogenemia, and higher insulin resistance is observed in T2D, but not in GD during pregnancy. Decreased estrogen and E/T ratio found in T2D and GD suggests a diminished aromatase activity during gestation. T2D and GD are associated with specific changes in sexual steroids and insulin resistance levels during pregnancy.

[Fatal neonatal sepsis caused by vertical transmission of Morganella morganii. Report of one case]. / Sepsis neonatal precoz causada por transmisión vertical de Morganella morganii, en un embarazo de término.

We report a term neonate who developed early-onset sepsis due to Morganella morganii. The child was vaginally delivered after a short labor, and presented signs of perinatal asphyxia. Blood cultures taken soon after birth and from mother's lochia were positive for this microorganism. The infection was unresponsive to treatment with cefotaxime, to which the microorganism was susceptible, and the infant died at 17 days of age. M morganii is an opportunistic and uncommon pathogen, causing disease mainly in patients with underlying illness or after surgery. It is a rare perinatal pathogen, causing severe disease in premature infants, in association with maternal chorioamnionitis and premature rupture of the membranes.

Sepsis neonatal precoz causada por transmisión vertical de Morganella morganii, en un embarazo de término / Fatal neonatal sepsis caused by vertical transmission of Morganella morganii. Report of one case

We report a term neonate who developed early-onset sepsis due to Morganella morganii. The child was vaginally delivered after a short labor, and presented signs of perinatal asphyxia. Blood cultures taken soon after birth and from mother's lochia were positive for this microorganism. The infection was unresponsive to treatment with cefotaxime, to which the microorganism was susceptible, and the infant died at 17 days of age. M morganii is an opportunistic and uncommon pathogen, causing disease mainly in patients with underlying illness or after surgery. It is a rare perinatal pathogen, causing severe disease in premature infants, in association with maternal chorioamnionitis and premature rupture of the membranes (RevMéd Chile 2009; 137: 1201-4).