Higher baseline heart rate variability in CCHS patients with progestin-associated recovery of hypercapnic ventilatory response.

After a fortuitous observation of two cases of chemosensitivity recovery in women with congenital central hypoventilation syndrome (CCHS) who took desogestrel, we aimed to evaluate the ventilatory response to hypercapnia of five CCHS patients with or without treatment consisting of desogestrel (DESO) or levonorgestrel (LEVO). Only two patients became responsive to hypercapnia under treatment, according to their basal vagal heart rate variability. These results suggest that heart rate variability may be promising tool to discriminate patients susceptible to become responsive to hypercapnia under DESO-LEVO treatment.Clinical Trials Identifier NCT01243697.

Long-Acting Reversible Etonogestrel Subdermal Implant in Adolescents.

Several effective contraceptive options are available for use by adolescents, including the long-acting reversible subdermal implant and intrauterine devices, which provide a high level of convenience, privacy, and effectiveness for an adolescent. Knowledge of all the effective birth control methods is essential for the pediatrician to be able to provide effective contraceptive counseling for an adolescent. An approach to counseling using a reproductive justice framework, which allows the provider and adolescent patient to engage in shared decision-making, is described. This article focuses on the long-acting reversible etonogestrel (ENG) subdermal implant for adolescents. The ENG implant is labeled for preventing pregnancy by suppressing ovulation. The ENG implant may also have a role in ameliorating dysmenorrhea and heavy menstrual bleeding. Postlabeling studies indicate that the ENG implant is effective for up to 5 years, although the device's labeling states effectivenessup to 3 years. The main contraindication to using the ENG implant is pregnancy itself. Safe initiation of the ENG implant is described, including an approach to determine whether an adolescent is pregnant. The main adverse effect of the ENG implant is an unpredictable bleeding pattern that is most often ameliorated by use of nonsteroidal anti-inflammatory medications, as well as estrogen, if not contraindicated for the patient. Details of the insertion and removal procedures, including potential complications, are described to enable the pediatrician to provide effective anticipatory guidance for the adolescent.

Serotonin and the ventilatory effects of etonogestrel, a gonane progestin, in a murine model of congenital central hypoventilation syndrome.

Introduction: Congenital Central Hypoventilation Syndrome, a rare disease caused by PHOX2B mutation, is associated with absent or blunted CO2/H+ chemosensitivity due to the dysfunction of PHOX2B neurons of the retrotrapezoid nucleus. No pharmacological treatment is available. Clinical observations have reported non-systematic CO2/H+ chemosensitivity recovery under desogestrel. Methods: Here, we used a preclinical model of Congenital Central Hypoventilation Syndrome, the retrotrapezoid nucleus conditional Phox2b mutant mouse, to investigate whether etonogestrel, the active metabolite of desogestrel, led to a restoration of chemosensitivity by acting on serotonin neurons known to be sensitive to etonogestrel, or retrotrapezoid nucleus PHOX2B residual cells that persist despite the mutation. The influence of etonogestrel on respiratory variables under hypercapnia was investigated using whole-body plethysmographic recording. The effect of etonogestrel, alone or combined with serotonin drugs, on the respiratory rhythm of medullary-spinal cord preparations from Phox2b mutants and wildtype mice was analyzed under metabolic acidosis. c-FOS, serotonin and PHOX2B were immunodetected. Serotonin metabolic pathways were characterized in the medulla oblongata by ultra-high-performance liquid chromatography. Results: We observed etonogestrel restored chemosensitivity in Phox2b mutants in a non-systematic way. Histological differences between Phox2b mutants with restored chemosensitivity and Phox2b mutant without restored chemosensitivity indicated greater activation of serotonin neurons of the raphe obscurus nucleus but no effect on retrotrapezoid nucleus PHOX2B residual cells. Finally, the increase in serotonergic signaling by the fluoxetine application modulated the respiratory effect of etonogestrel differently between Phox2b mutant mice and their WT littermates or WT OF1 mice, a result which parallels with differences in the functional state of serotonergic metabolic pathways between these different mice. Discussion: Our work thus highlights that serotonin systems were critically important for the occurrence of an etonogestrel-restoration, an element to consider in potential therapeutic intervention in Congenital Central Hypoventilation Syndrome patients.

One-year follow-up of immediate postpartum contraceptive implant insertion in adolescents.

PURPOSE: Our study aimed to evaluate the acceptability, adverse effects and continuation rates among adolescents who accepted the etonogestrel (ENG) subdermal implant and compared to adolescents who chose other methods during the immediate postpartum period before hospital discharge, with one year follow-up up. MATERIALS AND METHODS: We conducted a cohort non-randomised study at the Women's Hospital, University of Campinas. All women up to 19 years of age, who gave birth at the hospital between July 2019 and April 2020, were invited to participate and were offered the ENG-implant or the routine contraceptive methods. They were followed for one year postpartum. RESULTS: We included 100 teenagers and 72 accepted the ENG-implant. Students are more likely to accept the ENG-implant than non-students (PR: 1.25 [95%CI 0.99-1.59]). Up to one year of follow-up, survival analysis showed that the time of adherence to the method was longer for the ENG-implant users (p = 0.0049). More than 90% of the adolescents were satisfied with the implant; however, five requested early removal due to menstrual irregularity and local discomfort. CONCLUSION: Provision ENG-implant for adolescents in the immediate postpartum demonstrated high acceptance and ensured effective contraception. After one year, most of them were satisfied, with a high continuation rate and without unplanned pregnancies.

The progestin-only pills drospirenone 4 mg and desogestrel 0.075 mg as an option for the management of dysmenorrhea and mastodynia.

INTRODUCTION: Dysmenorrhea and mastodynia are the most common gynecologic pain causes in women of all ages and races during their reproductive life. The following study aimed to show the influence of two POP´s in the development of dysmenorrhea and mastodynia after nine months of use. MATERIAL AND METHODS: A total of 858 women with 6691 drospirenone (DRSP) cycles and 332 women with 2487 desogestrel (DSG) cycles were analyzed. Women included in this study were all child-bearing potentials, at risk of pregnancy, agreeing to use only the study medication for contraception for the duration of the study medication treatment, aged 18 to 45. RESULTS: At screening, 168 (19.6%) of the 858 patients using DRSP and 64 (19,3%) of the DSG patients reported that they had suffered from dysmenorrhea within six cycles prior to the first visit before starting with the medication. 20,2% of the DRSP and 10,9% of the DSG group had a sever dysmenorrhea. After 9 cycles this was reduced to 0,6% and 3,1% respectively. In total, 96 women (11.2%) in the DRSP and 49 (14,8%) experienced mastodynia within six cycles before the screening. Of these 91.6% in the DRSP group and 91,8% in the DSG group had no or mild mastodynoa at follow-up. DISCUSSION: The progestins 4 mg and desogestrel 0,075 mg showed a marked effect in the non-contraceptive aspects of dysmenorrhea and mastodynia so that new possibilities are opened for these two benign gynecological diseases. Future studies must reaffirm these first data.

Hormonal, apoptotic, proliferative and inflammatory markers' expression in Desogestrel-treated women with ovarian endometriosis.

Endometriosis is a relatively frequent pathology in gynecological practice. We performed an analysis to demonstrate the molecular changes that occur in endometriosis synthetic progestin-treated patients, hoping to sketch a possible pathophysiological pathway that will help us to better understand and treat this debilitating disease. We conducted a prospective study that included a group of 40 women, evaluated in our hospital between 2020-2021. We evaluated immunohistochemical tissue expression of estrogen receptor (ER), progesterone receptor (PR), B-cell lymphoma 2 (Bcl-2) protein, Ki-67, and serum levels of osteopontin (OPN) and vascular endothelial growth factor (VEGF) in patients with ovarian endometrioma with and without progestin treatment. Our study revealed that Desogestrel treatment increases OPN serum levels, PR and Bcl-2 tissue expression and reduces VEGF serum levels and Ki-67 tissue expression. The results we have obtained are very interesting because the serum levels of OPN seem to be more influenced by progestin treatment, than by endometriosis itself. The study we have conducted gives a molecular complex view of what endometriosis represents and on how Desogestrel treatment works.

The prevalence of Implanon discontinuation and associated factors among Ethiopian women: A systematic review and meta-analysis.

BACKGROUND: Implanon discontinuation before the recommended time is problematic, as it puts women at risk of unwanted pregnancies and unsafe abortions, along with negative maternal health outcomes. Although the magnitude and determinants of Implanon discontinuation have been studied in Ethiopia, the results were inconsistent, with significant variability. Hence, this systematic review and meta-analysis aimed at estimating the pooled prevalence of Implanon discontinuation and its determinants in Ethiopia. METHODS: A comprehensive search of studies published before 18 February 2022 was done using electronic databases such as PubMed, Embase, Google Scholar, Scopus, Web of Science, Science Direct, and Cochrane Library. The relevant data were extracted using a Microsoft Excel 2013 and analyzed using STATA Version 16. A random-effect meta-analysis model was used to compute pooled prevalence and odds ratio. The Cochrane Q test statistics and I2 tests were used to assess the heterogeneity of the included studies. A funnel plot, Begg's, and Egger's tests were used to check for the presence of publication bias. RESULTS: A total of 11 studies with 4320 study participants were included in this meta-analysis. The overall pooled prevalence of Implanon discontinuation in Ethiopia was found to be 32.62% (95% confidence interval = 24.10, 41.13). There was significant heterogeneity among the included studies (I2 = 97.4%, p < 0.001). However, there was no statistical evidence of publication bias (p = 0.533). Dissatisfied with service provision at the time of insertion (odds ratio = 3.92, 95% confidence interval = 1.54, 6.29), not having pre-insertion counseling (odds ratio = 2.98, 95% confidence interval = 1.91, 5.04), the absence of post-insertion follow-up (odds ratio = 4.03, 95% confidence interval = 2.17, 5.90), and the presence of side effects (odds ratio = 2.93, 95% confidence interval = 1.87, 3.98) were found to be determinants of Implanon discontinuation. CONCLUSION: According to this systematic review and meta-analysis, one-third of Ethiopian women discontinued Implanon before the recommended time (3 years). Program managers and service providers should consider using more evidence-based and participatory counseling approaches to enhance client satisfaction. Furthermore, family planning service delivery points should be equipped to manage and reassure women who are experiencing side effects.

Gongning granules plus low dose hormone in pubertal functional uterine hemorrhage: Analysis of hemodynamics and clinical efficacy.

To evaluate the clinical effect of Gongning granules combined with low-dose hormone therapy in pubertal dysfunctional uterine bleeding (PDUB) and its effect on uterine hemodynamics. A total of 164 PDUB patients who were treated in the gynecological outpatient department of our hospital from December 2018 to June 2020 were randomized into study group and control group, with 82 cases each. The control group received estrogen progesterone, and the study group received Gongning granules plus. The clinical efficacy and uterine arterial hemodynamics were compared. The clinical efficacy of the study group was superior to the control group (91.46% vs. 76.83%, P<0.05). The study group yielded shorter bleeding control time and complete hemostasis time than the control group (P<0.05). The amount of menstrual bleeding and duration of menstruation in both groups decreased significantly with time and the study group was significantly lower than the control group (all P<0.05). The endometrial thickness in the study group was significantly thinner than the control group, and the maximum follicle diameter was significantly longer than that in the control group (all P<0.05). After treatment, the platelet count, hemoglobin level of peripheral blood, uterine arterial blood flow and mean flow velocity in the study group were significantly higher than those in the control group (all P<0.05). In addition, there was no significant difference in adverse drug reaction (ADR) between the two groups (P>0.05). In PDUB patients, Gongning granules plus low-dose hormone can significantly relieve bleeding symptoms, improve hemodynamic status and has good safety.

Comparative evaluation of low-level light therapy and ethinyl estradiol and desogestrel combined oral contraceptive for clinical efficacy and regulation of serum biochemical parameters in primary dysmenorrhoea: a prospective randomised multicentre trial.

We aimed to compare low-level light therapy with oral contraceptive pills for pain relief and serum levels of nitric oxide and prostaglandin E2 in patients with primary dysmenorrhoea. This was a randomised, active comparator-controlled, multicentre study. In total, 156 patients were randomised to receive either low-level light therapy with light-emitting diodes (LED) applying on two acupoints, namely, conception vessel 4 (CV4) and CV6 or conventional treatment with oral Marvelon, 30 µg of ethinyl estradiol and 150 µg of desogestrel (DSG/EE), for three consecutive menstrual cycles. The main outcome was the proportion of patients who achieved 33% or more decrease in pain scores measured using the visual analogue scale, which was deemed as efficient rate. Absolute changes in visual analogue scale scores, serum levels of nitric oxide (assessed by nitrites and nitrates reflecting nitric oxide metabolism) and prostaglandin E2 (measured by enzyme-linked immunosorbent assay) were the secondary outcomes. A total of 135 patients completed the study (73 in the light therapy group and 62 in the DSG/EE group). The efficient rate at the end of treatment was comparable between the groups (73.6% vs. 85.7%, χ2 = 2.994, p = 0.084). A more significant reduction in pain scores was observed in the DSG/EE group (39.25% vs. 59.52%, p < 0.001). Serum levels of prostaglandin E2 significantly decreased from baseline but did not differ between groups (- 109.57 ± 3.99 pg/mL vs. - 118.11 ± 12.93 pg/mL, p = 0.51). Nitric oxide concentration remained stable in both groups. Low-level light therapy with LED-based device applied on acupuncture points CV4 and CV6 demonstrated a similar level of dysmenorrhoea pain reduction to DSG/EE combined contraceptive. Both treatment modalities achieved clinically meaningful levels of pain reduction. Registration on ClinicalTrials.gov: TRN: NCT03953716, Date: April 04, 2019.

Interactions between etonogestrel-releasing contraceptive implant and 3 antiretroviral regimens.

OBJECTIVES: Long-acting reversible contraceptives are effective contraceptives for women with HIV, but there are limited data on etonogestrel implant and antiretroviral therapy pharmacokinetic drug-drug interactions. We evaluated etonogestrel/antiretroviral therapy drug-drug interactions, and the effects of etonogestrel on ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, and efavirenz pharmacokinetics. STUDY DESIGN: We enrolled postpartum women using etonogestrel implants and receiving ritonavir-boosted-atazanavir, ritonavir-boosted-lopinavir, or efavirenz-based regimens between 2012 and 2015. Etonogestrel implants were inserted 2 to 12 weeks postpartum. We performed pharmacokinetic sampling pre-etonogestrel insertion and 6 to 7 weeks postinsertion. We measured antiretroviral concentrations pre and postetonogestrel insertion, and compared etonogestrel concentrations between antiretroviral regimens. We considered a minimum serum etonogestrel concentration of 90 pg/mL adequate for ovulation suppression. RESULTS: We collected pharmacokinetic data for 74 postpartum women, 22 on ritonavir-boosted-atazanavir, 26 on ritonavir-boosted-lopinavir, and 26 on efavirenz. The median serum concentrations of etonogestrel when co-administered were highest with etonogestrel/ritonavir-boosted-atazanavir (604 pg/mL) and etonogestrel/ritonavir-boosted-lopinavir (428 pg/mL), and lowest with etonogestrel/efavirenz (125 pg/mL); p < 0.001. Minimum concentration (Cmin) of ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were lower after etonogestrel implant insertion, but overall exposure, predose concentrations, clearance, and half-lives were unchanged. We found no significant change in efavirenz exposure after etonogestrel insertion. CONCLUSIONS: Unlike efavirenz, ritonavir-boosted-atazanavir and ritonavir-boosted-lopinavir were not associated with significant decreases in etonogestrel concentrations. Efavirenz was associated with a significant decrease in etonogestrel concentrations. IMPLICATIONS: The findings demonstrate no interactions between etonogestrel and ritonavir-boosted-lopinavir or ritonavir-boosted-atazanavir, but confirm the decreased efficacy of etonogestrel with efavirenz-based antiretrovirals. This information should be used to counsel women with HIV who desire long-acting reversible contraceptives.

Women's contraceptive choice following the use of Implanon NXT: Findings from a study in Durban, South Africa.

Implanon NXT was introduced in South Africa (SA) in 2014 to expand the contraceptive method mix. While studies have explored patterns of implant use, data on contraceptive choice following implant removal is limited. Here, we describe contraceptive choice among 120 women requesting Implanon NXT removal, between 2017 and 2018, at an urban reproductive health clinic in Durban, SA. Among women who used the implant for three years (n=91), >50% chose to reinsert Implanon NXT. Reasons for choosing to reinsert included satisfaction with the implant, the desire for a long-acting method and having had no side effects. A third of women chose not to reinsert Implanon NXT after three years due to side effects such as problematic bleeding. Most women requesting early removal of the implant switched to male condoms, injectables or oral contraceptives. Contraceptive services should provide women with contraceptive options and allow women to make informed decisions regarding contraceptive choice, in addition to providing support and managing side effects among Implanon NXT users.

Uterine pseudoaneurysm on the basis of deep infiltrating endometriosis during pregnancy-a case report.

BACKGROUND: Pseudoaneurysm of the uterine artery (UPA) is a rare cause of potentially life-threatening hemorrhage during pregnancy and puerperium. It is an uncommon condition that mainly occurs after traumatic injury to a vessel following pelvic surgical intervention, but also has been reported based on underlying endometriosis. There is an increased risk of developing UPA during pregnancy. Diagnosis includes clinical symptoms, with severe abdominal pain and is confirmed by sonographic or magnetic resonance imaging (MRI). Due to its potential risk of rupture, with a subsequent hypovolemic maternal shock and high fetal mortality, an interdisciplinary treatment should be considered expeditiously. CASE PRESENTATION: We present the case of a 34-year old pregnant symptomatic patient, where a large UPA was detected at 26 weeks, based on deep infiltrating endometriosis (DIE). The UPA was successfully treated by selective arterial embolization. After embolization, the pain decreased but the woman still required intravenous analgesics during follow-up. At 37 weeks she developed a sepsis from the intravenous catheter which led to a cesarean section and delivery of a healthy boy. She was discharged 10 days postpartum. CONCLUSIONS: UPA should be considered in pregnant women with severe abdominal and pelvic pain, once other obstetrical factors have been excluded. DIE might be the underlying diagnosis. It is a rare but potentially life-threatening condition for mother and fetus.

Acceptability of ENG-releasing subdermal implants among postpartum Brazilian young women during the COVID-19 pandemic.

OBJECTIVE: To evaluate etonogestrel (ENG)-implant acceptance during the immediate postnatal period among adolescents and young women during the COVID-19 pandemic, and to compare variables according to choice and discuss possible implications of this measure during the pandemic period. METHODS: A cross-sectional study was designed. All women aged up to 24 years, who delivered between April 25, 2020, and June 24, 2020, at Women's Hospital, University of Campinas, São Paulo, Brazil were considered. The ENG-implant or other contraceptive methods were offered prior to hospital discharge. The participants were split into two groups: (1) those who chose the ENG-implant and (2) those that refused the implant. Descriptive, bivariate, and multivariate analyses were performed. RESULTS: 151 women were included, with 76.2% selecting the ENG-implant. The average age was 19.5 years; 73.2% of pregnancies were unplanned, 32.5% already had a previous pregnancy, 74% were single, and 75.5% were not in full time education. Further, 70.5% had previously used contraceptives, with 89.1% unsatisfied with their previous method that opted for the ENG-implant (P = 0.07). CONCLUSION: Offering the ENG-implant to youths during the immediate postnatal period is evidence-based care, and contraceptive provision is an essential health promotion tool, even during a pandemic. Thinking quickly about public policies in times of crisis is important to guarantee sexual and reproductive rights.

A systematic review on clinical effectiveness, side-effect profile and meta-analysis on continuation rate of etonogestrel contraceptive implant.

BACKGROUND: Unintended pregnancies (UIP) have a significant impact on health of women and the health budget of countries. Contraception is an effective way to prevent UIPs. The study objective was to collate evidence on clinical effectiveness of etonogestrel subdermal implant (ESI), continuation rate and side effect profile among eligible women of reproductive age group, as compared to levonorgestrel intrauterine system (LNG-IUS), copper intrauterine device (Cu-IUD) and depot medroxy progesterone acetate injections; other types of contraceptive implants were excluded as comparators. METHODS: The protocol of the systematic review was registered in Prospero (registration number: CRD42018116580). MEDLINE via PubMed, Cochrane library and web of science were the electronic databases searched. A search strategy was formulated and studies from 1998 to 2019 were included. Clinical trial registries and grey literature search was done. Critical assessment of included studies was done using appropriate tools. A qualitative synthesis of included studies was done and a meta-analysis was conducted in RevMan software for continuation rates of ESI as compared to other long acting reversible contraceptives (LARC) e.g. LNG IUS and Cu-IUD. RESULTS: The search yielded 23,545 studies. After excluding 467 duplicates, 23,078 titles were screened and 51 studies were included for the review. Eight of the 15 studies reporting clinical effectiveness reported 100% effectiveness and overall pearl index ranged from 0 to 1.4. One-year continuation rates ranged from 57-97%; 44-95% at the end of second year and 25-78% by 3 years of use. Abnormal menstruation was the most commonly reported side effect. There was no significant difference in bone mineral density at 1 year follow-up. The meta-analyses showed that odds ratio (OR) of 1-year continuation rate was 1.55 (1.36, 1.76) for LNG-IUS vs. ESI and 1.34 (1.13, 1.58) for copper-IUD vs. ESI; showing that continuation rates at the end of one-year were higher in LNG-IUS and copper-IUD as compared to ESI. CONCLUSION: ESI is clinically effective and safe contraceptive method to use, yet 1-year continuation rates are lower as compared to LNG-IUS and copper-IUD, mostly attributed to the disturbances in the menstruation.