Cornual adenomyosis in Essure® device users and in patients hysterectomized for other causes: A retrospective cohort study.

OBJECTIVE: To determine whether adenomyosis is present in the cornual portion of hysterectomies of symptomatic sterilization device users and in patients hysterectomized for different benign causes and who presented with pelvic pain and/or menstrual alterations. METHODS: An observational, analytical, cross-sectional, single-center, retrospective cohort study was conducted in a secondary level hospital. Cohort 1 consisted of women who had Essure® hysteroscopic sterilization devices inserted between 2009 and 2017, who developed gynecologic symptoms (pelvic pain, heavy menstrual bleeding, and/or abnormal uterine bleeding) and who underwent a hysterectomy for explantation of the devices. Cohort 2 consisted of women with the same gynecologic symptoms, who underwent a hysterectomy for other benign causes. All surgeries were performed by the gynecology team between 2018 and 2022. A descriptive and comparative analysis of sociodemographic, clinical characteristics, and pathologic findings between cohorts was made. RESULTS: In total, 96 patients were studied (cohort 1 included 34 women, cohort 2 included 62 women). Pelvic pain was found to be more frequent in the cohort of Essure users (76.47% vs. 50%, P = 0.012), with a ratio of three times higher in this group (odds ratio 3.25, 95% confidence interval 1.27-8.28). Adenomyosis was more frequently found in the Essure group, both at corporal and cornual portions, the latter being five times higher in this cohort (relative risk = 5.47; 95% confidence interval 1.17-25.64). CONCLUSIONS: The present study may be the first to describe cornual adenomyosis related to Essure devices. These devices may play a role in the development of adenomyosis and, consequently, pelvic pain. However, causality is difficult to establish.

Effects of commercial amniotic membrane extract on the re-epithelialization time and the early expression of matrix metalloproteinase-9 in cats with experimentally induced corneal ulcers.

OBJECTIVES: To investigate whether a commercially available amniotic membrane extract (AME) can accelerate corneal wound healing and suppress the early expression of MMP-9 in the tears of cats with experimentally induced superficial ulcerative keratitis. PROCEDURES: A total number of 16 cats were included. At the end of keratectomy, cats in the treatment group (TG, n = 8) received 40 µl of AME (EyeQ® Amniotic Eye Drops, Vetrix®) four times daily, while cats in the control group (CG, n = 8) received 40 µl of saline at the same time points. Tears were collected 24 and 48 h after keratectomy, and the total MMP-9 was quantified by ELISA. RESULTS: The corneal re-epithelialization rate did not differ between groups (p = .26), being 0.48 ± 0.05 mm2 /h in the CG and 0.41 ± 0.03 mm2 /h in the TG. Similarly, the average time to achieve corneal wound healing did not differ between groups (p = .25) and was 61.50 ± 3.54 h in the CG and 70.50 ± 6.71 h in the TG. The dimensions of the ulcerated areas also did not differ at any time point between the groups (p > .05). In both groups, corneas healed without scarring, pigmentation, or vascularization. The expression of MMP-9 in the tears was similar in both groups at 24 h post-keratectomy, with a slight decrease at 48 h (p > .05). CONCLUSIONS: The instillation of a commercial AME (EyeQ®) is safe, but it did not decrease the corneal re-epithelialization time or the early expression of MMP-9 in the tears of cats with experimentally induced superficial ulcerative keratitis in this study.

Analysis of clinical data associated with Essure® sterilization devices: An expanded case series.

OBJECTIVES: To evaluate clinical data in women who underwent Essure® hysteroscopic sterilization and to determine whether this sterilization technique plays a role in developing new-onset symptoms. STUDY DESIGN: An observational, retrospective, single-center study. It was conducted in a secondary level hospital. It included 804 women who had Essure® hysteroscopic sterilization from 2009 to 2017. Charts from these women were reviewed from June 2009 to November 2019, searching for the development of gynecological symptoms (pelvic pain and bleeding disorders) and non-gynecological symptoms (bloating, joint pain, fatigue, headache, alopecia, allergy and depression). The sample was divided into two groups depending on whether they had developed gynecological symptoms (symptomatic group) or not (asymptomatic group), and a descriptive and comparative analysis was made between them. The impact of the global social alarm in 2015 regarding adverse events attributed to the devices, the development of non-gynecological symptoms, and the treatments required, including conservative and surgical options, were also described. RESULTS: Out of 804 women who had Essure® devices placed, 541(67.29%) remained asymptomatic, 263(32.71%) developed gynecological symptoms, and 41 of these (15.5% of the total sample) requested Essure® surgical removal. Pelvic pain was the most frequent symptom and the main reason for surgical removal. Bleeding alterations were the second most frequent symptom. Up to 55.89% described the symptoms after the social alarm. Non-gynecological symptoms were statistically significantly more frequent in the symptomatic group. CONCLUSIONS: More than a half of the women who underwent Essure® sterilization remained asymptomatic. The new-onset symptoms attributed to the devices are the minority and causality is difficult to establish. IMPLICATIONS STATEMENT: Our research provides new follow-up data about Essure® hysteroscopic sterilization. Association between gynecological symptoms and Essure® devices is difficult to demonstrate and some confounding factors may be implicated. The results we described, may guide and counsel medical-patient decisions for the treatment of symptoms related to the devices, including surgical removal.

Cervical adenocarcinoma in situ during pregnancy and subsequent fertility-sparing therapy challenge.

OBJECTIVE: Adenocarcinoma in situ (AIS) of the cervix is a premalignant lesion, and a precursor of invasive disease. It is less frequent than its squamous counterpart. During pregnancy, AIS is a scarcely described scenario, whose diagnosis barely differs from non-pregnant patients. Its management is challenging with hysterectomy being the definitive treatment. However, its high incidence in young patients makes fertility-sparing management an approachable option for selected patients. The objective of this study is twofold. Firstly, we describe a case of a patient with AIS during pregnancy and the postpartum period. Secondly, the available literature is reviewed. METHODS: Retrospective medical record review of a single case and a medical literature search in Pubmed of AIS cases in pregnant women. RESULTS: A 31-year-old woman with cervical AIS diagnosed during pregnancy underwent serial fertility-sparing surgeries including a loop electrosurgical excision procedure and endocervical curettage during the second trimester, and a re-conization and a simple traquelectomy during the postpartum period, until negative margins were achieved. Upon reviewing the literature from 1965 to 2020, 23 other cases were found. CONCLUSION: Surgical management of cervical AIS during pregnancy is a safe procedure. Subsequent conservative surgeries imply a real challenge to preserve fertility.

Male perception about the inconveniences associated with monthly bleeding for their partner - an international survey.

OBJECTIVE: To assess men's perceptions about monthly bleeding and associated inconveniences for their partner, as well as men's attitudes regarding the desired menstruation frequency for their partner and knowledge about hormonal contraceptives. METHODS: A 15 min quantitative online survey was conducted among 5044 men aged 18-45 years, who had been in a relationship for more than 6 months, across 13 European countries (Austria, Belgium, Czech Republic, France, Germany, Hungary, Italy, Latvia, The Netherlands, Poland, Portugal, Spain and Switzerland). Responses were compared to those obtained in a similar study among European women. RESULTS: Most men perceived that their partner considered her menstrual flow as moderate, lasting an average of 5.2 d, slightly longer than previously reported by women. Almost all men reported that their partners experience menstruation-related symptoms. However, prevalence of mood-related symptoms was perceived to be more frequent and physical symptoms less frequent, relative to women's self-reported symptoms. Given the option, 71% of men would choose longer intervals between their partner's periods. Maintaining the couple's sex life, social life and relationship quality were key factors cited in their preference. Overall, 42% of respondents stated that women taking hormonal contraceptives needed to have monthly periods. CONCLUSIONS: Men's perception regarding their partner's periods was generally consistent with that previously reported by women. Most men would prefer less frequent bleeding episodes for their partners. Although, the present data suggest that couples are discussing periods, knowledge about contraception could be improved. Health care professionals should intensify counselling to better inform both partners about their contraceptive options.

The inconvenience due to women's monthly bleeding (ISY) survey: a study of premenstrual symptoms among 5728 women in Europe.

OBJECTIVES: The aim of the ISY study was to investigate the prevalence of menstrual-related symptoms prior to and/or during menstrual or withdrawal bleeding among women from 12 European countries. METHODS: A 15-min quantitative online survey was conducted in two waves from February to September 2015 among 5728 women aged between 18 and 45 years, with an equal distribution of women using a combined hormonal contraceptive, including regular combined oral contraceptives (COCs) (CHC group, n = 2739) and women using a non-hormonal contraceptive or no contraceptive (non-HC group, n = 2989). RESULTS: The prevalence of at least one menstrual-related symptom was high in CHC users (93%) and in non-HC users (95%) (p < .0001) and the average number of symptoms reported was 5.3 vs. 5.9, respectively, (p < .0001). Pelvic pain, bloating/swelling, irritability and mood swing were reported in more than half of the women in both groups. Although generally modest, symptom severity was higher in non-HC users, except for headache. Overall, during the last four cycles, 60-75% of women did not require a treatment for most symptoms but headaches and pelvic pain. Mood swings/irritability, water retention/weight gain, lack of energy/mood swings and lack of energy/irritability were common symptoms that frequently co-occurred. No associations were reported between symptoms and age, educational qualifications or women's desire to reduce the frequency of menstruation. CONCLUSIONS: Premenstrual and menstrual symptomatology was less frequent, less numerous and less severe (except for headache) in women using CHCs; however, it remains a common concern. Reducing the frequency of menstrual periods could reduce withdrawal-related symptoms.

Women's preferences for menstrual bleeding frequency in 12 European countries: the Inconvenience Due to Women's Monthly Bleeding (ISY) survey.

OBJECTIVES: Our aim was to assess the level of inconvenience associated with menstrual bleeding and determine how many women across 12 European countries would prefer a bleeding frequency of less than once a month and what would motivate their choice. METHODS: A 15-min quantitative online survey was conducted in two waves among 5728 women aged between 18 and 45 years, with an equal distribution of women using a combined hormonal contraceptive (CHC group, n = 2739) and women using a non-hormonal contraceptive or no contraceptive (non-HC group, n = 2989). The first wave was carried out in Austria, Belgium, France, Italy, Poland and Spain, in February 2015, and the results have been published. The second wave was conducted in the Czech Republic, Germany, Hungary, Portugal, Latvia and the Netherlands, between August and September 2015. RESULTS: The menstrual period was significantly longer (5.0 versus 4.6 days) and heavier (15 versus 7%) in non-HC users than in CHC users (p < .0001). Given the choice, ∼60% of women would like less frequent menstrual bleeding. There was heterogeneity in the preference across countries. Sexuality, social life, work and sporting activities were key factors affecting women's preference. CONCLUSION: The majority of women in the 12 European countries would prefer to reduce the frequency of menstrual periods. Quality of life was the main factor affecting their preference.

Missed pills: frequency, reasons, consequences and solutions.

OBJECTIVES: Oral hormonal contraception is an effective contraceptive method as long as regular daily intake is maintained. However, a daily routine is a constraint for many women and can lead to missed pills, pill discontinuation and/or unintended pregnancy. This article describes the frequency of inconsistent use, the consequences, the risk factors and the possible solutions. METHODS: The article comprises a narrative review of the literature. RESULTS: Forgetting one to three pills per cycle is a frequent problem among 15-51% of users, generally adolescents. The reasons for this are age, inability to establish a routine, pill unavailability, side effects, loss of motivation and lack of involvement in the initial decision to use oral contraceptives. The consequences are 'escape ovulations' and, possibly, unintended pregnancy. Solutions are either to use a long-acting method or, for women who prefer to take oral contraceptives, use a continuous or long-cycle regimen to reduce the risks of follicular development and thus the likelihood of ovulation and unintended pregnancy. A progestogen with a long half-life can increase ovarian suppression. CONCLUSIONS: For women deciding to use oral contraceptives, a shortened or eliminated hormone-free interval and a progestogen with a long half-life may be an option to reduce the negative consequences of missed oral contraceptive pills.

Women's preferences for menstrual bleeding frequency: results of the Inconvenience Due to Women's Monthly Bleeding (ISY) survey.

OBJECTIVES: Our aim was to assess the level of inconvenience associated with monthly bleeding, determine how many women would prefer a bleeding frequency of less than once a month, and what would motivate their choice. METHODS: A 15-min quantitative online survey was carried out among 2883 women aged between 18 and 45 years in six European countries (Austria, Belgium, France, Italy, Poland and Spain). RESULTS: Of those surveyed, 1319 women used a combined hormonal contraceptive (CHC group) and 1564 used a non-hormonal contraceptive or no contraceptive (non-HC group). The menstrual period was significantly longer (5 vs. 4.5 days), heavier (16% vs. 8% heavy menstrual flow) and associated with more symptoms (6.1 vs. 5.6) in non-HC users than in CHC users (p < 0.0001). More than half of the women in each group reported pelvic pain, bloating/swelling, mood swings and irritability, but the rate was significantly higher in the non-HC group. Given the choice, 57% of women in both groups said they would opt for longer intervals between periods. Sexuality, social life, work and sporting activities were key factors affecting their decision. CONCLUSIONS: The majority of women would prefer to have menstrual periods less than once a month, with a frequency ranging from once every 3 months to no periods at all. This can be explained by the desire to avoid the unpleasant aspects of menstruation and its negative impact on private and professional life.

Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel-containing ethinylestradiol pills: A literature review.

OBJECTIVE: Since its introduction 50 years ago, the contraceptive pill has continuously evolved to decrease the risk of venous thromboembolism (VTE) associated with its use. An increased risk of VTE still remains, however. Other concerns, such as effects on lipid and carbohydrate metabolism, have also been reported. In this study we compared two reference combined oral contraceptives (COCs) containing ethinylestradiol (EE)/levonorgestrel (LNG) and EE/drospirenone (DRSP) with COCs containing estradiol (E2) (estradiol valerate [E2V]/dienogest [DNG] and E2/nomegestrol acetate [NOMAC]). They were evaluated according to their influence on recognised haemostatic and metabolic markers. METHODS: A literature search of the MEDLINE/PubMed database was conducted for head-to-head studies. EE/LNG was chosen as the comparator pill. RESULTS: The haemostatic impact of E2 pills and EE/LNG has been extensively compared, in contrast to that of EE/DRSP and EE/LNG. Changes in haemostatic and metabolic marker levels between EE/LNG and E2V/DNG were generally not statistically significant. E2/NOMAC showed statistically significantly favourable results on haemostatic markers and had a neutral effect on carbohydrate and lipid metabolism when compared with EE/LNG. CONCLUSION: E2/NOMAC exhibits less haemostatic and metabolic impact than EE/LNG and other COCs, suggesting that it may be a promising candidate to reduce residual VTE risk associated with COC use. Confirmation from a well-powered prospective clinical trial is, however, needed.

Extended regimens of combined hormonal contraception to reduce symptoms related to withdrawal bleeding and the hormone-free interval: a systematic review of randomised and observational studies.

OBJECTIVE: To assess whether continuous and extended regimens (CRs/ERs) of combined hormonal contraceptives (CHCs) improve symptoms related to withdrawal bleeding or the hormone-free interval and to compare the efficacy, safety, and cost of CRs/ERs to those of conventional 28-day regimens. STUDY DESIGN: A literature search of the PubMed database was conducted for randomised clinical trials (RCTs) and observational studies published in any language between 2006 and 2013. RESULTS: Sixteen RCTs and 14 observational studies evaluated issues related to our objectives. CRs/ERs, whose efficacy and safety were comparable to those described for conventional regimens, were preferred due to their improvement of symptoms related to withdrawal bleeding or the hormone-free interval and the lower costs resulting from the reduced incidence of these symptoms. CONCLUSION: The contraceptive efficacy and safety of CR/ER use of CHCs is at least equal to that of 28-days conventional regimens, and this use may have some cost savings. CRs/ERs are recommended for women willing to take a CHC for treatment of symptoms related to withdrawal bleeding or the hormone-free interval.

Toward a new concept of "natural balance" in oral estroprogestin contraception.

The Pill has undergone many changes since its first appearance some 50 years ago. Key developments included the reduction of ethinylestradiol doses and the synthesis of new progestins in order to increase safety, compliance and efficiency. Low-dose combined oral contraceptives (COCs) are currently the preferred option for millions of women. Due to this widespread use, it has been argued that the safety of COCs should be even better, raising the threshold for excellence. Yet in spite of major improvements, there is still an associated risk of venous thromboembolism (VTE). The next step in COCs' evolution should take total estrogenicity and hepatic estro-androgenic balance into account. The focus on the estrogen component--which has not changed in 50 years--has yielded a new class of natural estrogen pills. Following the introduction of a first quadriphasic pill, a monophasic estradiol pill based on the concept of "natural balance" was subsequently made available. These recent achievements could represent a step forward in the evolution of COCs and pave the way for better safety.

Continuation rate of combined hormonal contraception: a prospective multicenter study.

BACKGROUND: Data from clinical trials regarding continuation of use and contraceptive efficacy do not always apply to the general public. Therefore, a study among typical users was conducted to assess the continuation rate at the end of 12 cycles of combined hormonal contraceptive methods, reasons for discontinuation, and the Pearl index. METHODS: Prospective, observational, and multicenter study of 3443 women aged 18 to 49 years starting one of the three combined hormonal contraception methods available in Spain (the vaginal ring, the contraceptive pill, and the transdermal skin patch). RESULTS: The study population (intention-to-treat analysis) included 3443 women, of whom 45.4% were included in the vaginal ring group, 42.6% the pill group, and 12.1% the skin patch group. The continuation rate at 12 cycles was 45.9% for the pill, 42.3% for the vaginal ring, and 26.0% for the skin patch. The Pearl index was 0.61 (95% confidence interval [CI] 0-1.2) for the pill, 0.61 (95% CI 0-1.1) for the vaginal ring, and 2.34 (95% CI 0.3-9) for the skin patch (p<0.001). CONCLUSION: At 12 cycles, the vaginal ring and the pill showed similar continuation rates and effectiveness, which were significantly higher than the skin patch.

Comparison of sublingual versus vaginal misoprostol for second-trimester pregnancy termination: a meta-analysis.

BACKGROUND: The development of safe and effective techniques for second-trimester abortion (associated or not with fetal death) has become a major clinical challenge. AIMS: To compare the efficacy and safety of sublingual versus vaginal misoprostol for mid-trimester pregnancy termination. METHODS: We conducted a meta-analysis of published randomised controlled trials that compared sublingual and vaginal routes. Primary outcome measures were complete abortion rate at 24 and 48 h and induction-abortion interval, and the secondary outcome measures were side effects and patients' preference for the route. Pooled risk ratios were calculated for categorical variables, and continuous variables were compared by means of weighted mean differences. RESULTS: Both routes' efficacy was similar following 24 h of treatment (pooled RR 1.04, 95% CI 0.93-1.7). Successful induction percentage after 24 h was significantly higher in nulliparous women with vaginal misoprostol (pooled RR 0.78; 95% CI 0.71-0.87). The efficacy after 48 h was significantly greater with vaginal misoprostol in the general population (pooled RR 0.96; 95% CI 0.93-0.99) and in nulliparous women (pooled RR 0.89; 95% CI 0.86-0.95). The sublingual route shortened the induction-fetal expulsion interval (WMD -4.54, 95% CI -8.03 to -1.05) and was the route preferred among women. No statistically significant differences between treatment groups were observed for placental retention or for any side effect except for fever, which was more common in the vaginal group. CONCLUSIONS: Sublingual and vaginal misoprostol are safe and effective for mid-trimester pregnancy termination. The differences obtained between both routes probably do not have clinical consequences.