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This case report highlights serious permanent sequelae of a malpositioned levonorgestrel intrauterine device. Initial cervical injury resulted in fistula formation and large hematoma eventually requiring hysterectomy. Uterine depth less than 5.5 cm should prompt timely evaluation, and immediate replacement is not advised when there is concern for injury. [ABSTRACT FROM AUTHOR]

Objectives: To determine if PF-88, a reverse thermo-responsive polymer designed to create a gel at body temperature and liquefy at a lower temperature (21°C) can reversibly occlude the fallopian tubes in rabbits.Study Design: Mature female New Zealand White rabbits underwent laparotomy and placement of 22-gage catheter into the lumen of the distil uterine horns for evaluation of tubal patency by fluoroscopy using radio opaque contrast and treatment with PF-88. In the Acute Phase group (n = 5) after PF-88 treatment we immediately cooled the serosal surface of the tube with ice for 90 seconds to liquify the gel then reassessed patency. In the Survival Phase groups, animals recovered from the initial surgery and then underwent a second procedure for evaluation of tubal occlusion and reversibility at 4 (n = 3), 14 (n = 2), and 28 (n = 3) weeks after the initial procedure. We compared the histologic appearance of the treated fallopian tubes to untreated controls (n = 3).Results: In the Acute Phase, we found all 10 fallopian tubes patent on initial evaluation, occluded following treatment with PF88, and patent following re-liquification by chilling. Animals in the Survival Group, all but one of the treated tubes appeared blocked at follow-up and patent following chilling. The treatment failure occurred in an animal in the 4-week group. Tubes treated with PF88 showed no histologic evidence of residual material or damage after removal of the polymer.Conclusion: The PF-88 reverse thermo-responsive polymer demonstrated the ability to reversibly block fallopian tubes for up to 28 weeks.Implications: The demonstration of reversible occlusion of the fallopian tube of rabbits using PF-88, a thermo-responsive reverse polymer, support additional studies to evaluate the potential of this polymer as a contraceptive in women. [ABSTRACT FROM AUTHOR]

Objective: To evaluate differences based on intrauterine device (IUD) frame geometry in force, and stress, and strain at the stem/arms junction during simulated IUD removal., Study Design: We manufactured injection-molded frame models for three Nova-T IUDs (Mirena [model M]; Liletta [model L]; Kyleena [model K]) and a Tatum-T IUD (Paragard [model P]) at two-times scaling. We created a custom fixture to simulate the uterus and used a screw-driven machine to pull models at various displacement rates through the 10 cm fixture cavity to measure force and strain and calculate stress at the IUD stem/arms junction. We tested models at 30 mm/min and higher displacement rates for exploratory analyses. We used Mann-Whitney U test for statistical testing., Results: We completed testing at 30 mm/min using five of each Nova-T model and nine model P samples. Resistance against the cavity walls created significantly more force on model P (11.83, interquartile range [IQR] 11.61-12.31) than any Nova-T model samples (p < 0.001). The smaller model K created slightly more median stress (MPa) than the larger model M (0.36 [IQR 0.33-0.38] and 0.79 [IQR 0.76-0.80], respectively, p = 0.008); model P samples generated significantly more median stress than other models (1.70 [IQR 1.67-1.77], p < 0.001). Strain plots demonstrated permanent deformation for some samples during IUD removal simulation. We tested 20 samples at various higher displacement rates up to 2500 mm/min, with stress notably increasing for model P samples with increasing rates. No fractures occurred., Conclusions: Force and stress at the stem/arms junction are higher with Tatum-T-shaped compared to Nova-T-shaped IUD models under the same testing conditions, and a higher speed of extraction causes more stress., Implications: Sharp corners create vulnerability under static and fatigue loading in structural components due to increased local stresses. Our findings suggest that IUDs with Tatum-T frames should be removed slowly to minimize the stress at the stem/arms junction. Future studies can provide more information if performed with commercially available products., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The primary objective was to measure IUD-fundus and IUD-myometrium distances by ultrasound of IUDs placed during cesarean section over the first year of use. The secondary objective was to determine if these distances are associated with risk of expulsion or removal for side effects.Study Design: In this prospective observational study, we performed ultrasounds at six - ten weeks, three months and one year postpartum to measure the distance from the top of the device to the fundal serosa (IUD-fundus) and upper margin of the endometrial cavity (IUD-myometrium). We also assessed IUD expulsion or discontinuation for side effects at each visit.Results: We enrolled 93 women who had copper (n = 77) or levonorgestrel (n = 16) IUDs placed at time of cesarean section. Two patients had complete expulsion, six had partial expulsion and nine requested removal for symptoms. Overall, median IUD-fundus measurements were 2.13 cm (IQR 1.87-2.55) at 6-10 weeks, 1.87 cm (IQR 1.53-2.23) at 3-months and 2.02 cm (IQR 1.67-2.40) at 1-year. Among copper IUD users, distances at six weeks and three months were similar in women who did or did not have expulsion or removal at one year however small numbers limit our ability to assess this relationship.Conclusion: We describe the location on ultrasound of IUDs placed at the time of Cesarean section over the first year. We found similar IUD locations at six weeks and three months for participants who did or did not experience expulsion or removal by one year.Implications: Position of intrauterine devices placed during cesarean section was similar for those who did or did not have expulsion or removal for symptoms in the first year after placement. These data may help in the design of future studies to determine if ultrasound measurement of IUDs predicts IUD complications. [ABSTRACT FROM AUTHOR]

Hemorrhage after abortion is rare, occurring in fewer than 1% of abortions, but associated morbidity may be significant. Although medication abortion is associated with more bleeding than procedural abortion, overall bleeding for the two methods is minimal and not clinically different. Hemorrhage can be caused by atony, coagulopathy, and abnormal placentation, as well as by such procedure complications as perforation, cervical laceration, and retained tissue. Evidence for practices around postabortion hemorrhage is extremely limited. The Society of Family Planning recommends preoperative identification of individuals at high risk of hemorrhage as well as development of an organized approach to treatment. Specifically, individuals with a uterine scar and complete placenta previa seeking abortion at gestations after the first trimester should be evaluated for placenta accreta spectrum. For those at high risk of hemorrhage, referral to a higher-acuity center should be considered. We propose an algorithm for treating postabortion hemorrhage as follows: (1) assessment and examination, (2) uterine massage and medical therapy, (3) resuscitative measures with laboratory evaluation and possible reaspiration or balloon tamponade, and (4) interventions such as embolization and surgery. Evidence supports the use of oxytocin as prophylaxis for bleeding with dilation and evacuation; methylergonovine prophylaxis, however, is associated with more bleeding at the time of dilation and evacuation. Future research is needed on tranexamic acid as prophylaxis and treatment and misoprostol as prophylaxis. Structural inequities contribute to bleeding risk. Acknowledging how our policies hinder or remedy health inequities is essential when developing new guidelines and approaches to clinical services., (Copyright © 2023. Published by Elsevier Inc.)

Cervical preparation with laminaria reduces complications with 2nd trimester dilation and evacuation. During a surgical abortion at 22 weeks, we could not remove laminaria manually or with ring forceps due to laminaria "dumbbelling" [1]. Without pushing laminaria into the uterus, we mechanically dilated the cervix and removed the incarcerated laminaria. [ABSTRACT FROM AUTHOR]

We report a case of severe systemic delayed dermatitis in a patient with nickel-titanium sterilization microinserts placement complicated by uterine perforation and polyethylene terephthalate (PET) exposure. We hypothesize that delayed dermatitis may be caused by the exposure of PET fibers in this patient with underlying autoimmune disorder. Further research on the use of PET and the potential of systemic dermatologic reactions when exposure occurs is needed, especially when considering the inclusion of PET in future implant device development. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine predictors of uterine evacuation for women undergoing medical abortion using mifepristone and vaginal misoprostol through 63 days' gestation.Study Design: We pooled data from two prospective multicenter medical abortion trials. In one study, women received mifepristone 200 mg followed either 6-8 or 23-25 h later by misoprostol 800 mcg vaginally. In the second study, women received mifepristone 200 mg followed either <15 min or 23-25 h later by misoprostol 800 mcg vaginally. We examined the absolute risk (AR) of uterine evacuation using Fisher's Exact Tests for categorical variables and Student t test and Wilcoxon rank-sum tests for continuous variables. We used logistic regression to calculate odds ratios (ORs) of uterine evacuation.Results: Uterine evacuation was performed for 75 (3.5%) of 2160 women. In multivariable analysis, 5 or more prior deliveries (AR 11.9%, OR 4.6) and gestational age of 8 weeks or more (AR 4.1%, OR 2.1) were significantly associated with uterine evacuation, while age of 20 years or younger (AR 1.4%, OR 0.4) was significantly and inversely associated with uterine evacuation. Prior cesarean delivery, multiple gestations, smoking, weight, body surface area and body mass index were not predictive of uterine evacuation in univariate or multivariable analysis.Conclusion: Uterine evacuation is an uncommon outcome in medical abortion with mifepristone and vaginal misoprostol. Five or more deliveries are the only significant predictor that identifies a group with an AR of uterine evacuation of more than 6%.Implications: Uterine evacuation is uncommon in medical abortion with mifepristone and vaginal misoprostol. Parity of five or more is the only significant predictor of uterine evacuation exceeding 6%. Until additional research is completed, medical abortion should not be withheld from women with five or more deliveries. [ABSTRACT FROM AUTHOR]

Introduction: This study compares the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a low-dose combined oral contraceptive (COC) in reducing adenomyosis-related pain and bleeding.Materials and Methods: A randomized clinical trial included 62 participants complaining of pain and bleeding that was associated with adenomyosis. Participants were randomly assigned to either LNG-IUS or COC treatment. The outcomes included the improvement of pain using a visual analogue scale, menstrual blood loss using a menstrual diary and estimated uterine volume by ultrasound for 6 months of treatment. We also compared uterine arteries and intramyometrial Doppler indices before and 6 months after treatment with both LNG-IUS and COCs.Results: Both treatments significantly reduced pain after 6 months of use; however, the reduction was greater in the LNG-IUS group (from 6.23±0.67 to 1.68±1.25) compared with the COCs group (from 6.55±0.68 to 3.90±0.54). Both treatment arms significantly decreased the number of bleeding days, uterine volume and Doppler blood flow in the uterus from before to after treatment. These effects were more significant in the LNG-IUS arm compared with the COC arm.Conclusion: Both LNG-IUS and COCs decreased the pain and menstrual bleeding that is associated with adenomyosis. However, LNG-IUS is more effective than the COCs in reducing pain and menstrual blood loss. This effect may be secondary to the decrease in uterine volume and the increase in blood flow resistance. [ABSTRACT FROM AUTHOR]

Abstract: Background: Leukemia inhibitory factor (LIF) is a cytokine with an essential role in the preparation of the endometrium for implantation. Previous studies demonstrated that PEGLA, a LIF receptor antagonist (LA) conjugated with polyethylene glycol (PEG), effectively prevents implantation in mice, identifying PEGLA as a potential contraceptive for women. Study Design: Adult female cynomolgus macaques were used to determine the optimal route of administration to deliver PEGLA to the uterine endometrium. Endometrial explants were used to examine the ability of PEGLA to block LIF action at endometrial cells. Results: Both intramuscular and subcutaneous PEGLA administration resulted in peak serum PEGLA 24 h after administration; serum PEGLA was detectable throughout the 144-h sampling period. In contrast, serum PEGLA was near or below the limit of detection after vaginal administration. After intramuscular administration, PEGLA was localized to both luminal and glandular epithelial cells of the uterine endometrium, and PEGLA was measurable in endometrial lysates. PEGLA administration reduced endometrial signal transducer and activator of transcription protein 3 (STAT3) phosphorylation in vivo and in vitro. PEGLA also blocked LIF's ability to elevate expression of cochlin, insulin-like growth factor-binding protein 3, vascular endothelial growth factor A, and cyclooxygenase-2 (also known as PTGS2) in endometrial explants in vitro. Conclusions: PEGLA was delivered to the non-human primate uterine endometrium with systemic administration, and PEGLA blocked LIF actions associated with implantation. Blocking LIF receptor activity with the antagonist PEGLA may prevent pregnancy in women and provide a novel alternative to currently-available hormonal and barrier contraceptives. [Copyright &y& Elsevier]

Abstract: Background: Evaluation of the efficacy of a novel medical device for removal of retained intrauterine devices (IUDs) under direct vision without uterine distention is reported. Cases: The five cases presented used the novel medical device to remove the IUDs. One woman had an incarcerated IUD, two women had fractured IUDs and two women had IUDs with lost threads. All IUDs were removed completely with use of direct vision without uterine distention. Conclusions: The device is effective for the removal of incarceration IUDs under direct vision without uterine distention. [Copyright &y& Elsevier]

Background: Postplacental intrauterine device (IUD) insertion is a safe, convenient and effective option for postpartum contraception. Few studies involve ultrasound-guided insertion, and none involve the levonorgestrel IUD or take place in the United States. Study Design: The study was conducted to assess the safety and feasibility of ultrasound-guided postplacental insertion of the levonorgestrel IUD following vaginal delivery in a U.S. residency program. Levonorgestrel IUDs were inserted under ultrasound guidance within 10 min of placental delivery by hand or using ring forceps. Subjects were examined at 4 and 10 weeks postpartum for evidence of expulsion or infection. Results: Thirty-four subjects were enrolled and 20 received an IUD. Follow-up data are available for 19 subjects over the 10-week follow-up period; 16 subjects returned for the 4-week follow-up, and 14 returned at 10 weeks. Two additional subjects could be contacted by telephone only. At 4 and 10 weeks postpartum, no subjects had evidence of infection. There were two expulsions (2/19, 10.5%) by 10 weeks postpartum. None of the subjects examined had a partial expulsion (intracervical location of the IUD). Conclusions: In this pilot study, ultrasound-guided postplacental insertion of the levonorgestrel IUD was feasible and not associated with infection. The risk of expulsion was acceptable. Ultrasound-guided postplacental insertion of the levonorgestrel IUD may be an alternative to delayed insertion but warrants further study. [ABSTRACT FROM AUTHOR]

Background: The study was conducted to investigate the inhibitory effect of 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) on embryo implantation in mice with a view to identifying whether it might be a suitable agent for postcoital contraception.Study Design: The anti-implantation efficacy of AEBSF was determined by counting the number of visible implanted embryos on Day 8 of pregnancy following a single intrauterine injection of AEBSF at doses of 30, 300 and 3000 microg per mouse uterine horn on Day 3 of pregnancy. The reversibility of the inhibitory effect of AEBSF on implantation was further evaluated by observing the outcome of a subsequent pregnancy without AEBSF treatment.Results: A dose-dependent inhibitory effect of AEBSF on embryo implantation in vivo was observed. Morphological analysis revealed no significant cytotoxicity of AEBSF on the mouse uterine epithelia. Furthermore, the anti-implantation effect of AEBSF was reversible.Conclusion: Intrauterine administration of AEBSF at an appropriate dose might provide a basis for the development of novel contraception. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study was conducted to determine the prevalence of Chlamydia trachomatis (CT) in the endometrium of depot medroxyprogesterone acetate (DMPA) users with and without breakthrough bleeding (BTB) (unscheduled bleeding) and/or chronic endometritis (CE). Methods: Cross-sectional study. Endometrial biopsies were performed on 20 DMPA users who were having BTB and 20 DMPA users who were amenorrheic. The paraffin-embedded tissue sections were washed with xylene and ethanol to remove the paraffin. CT was identified in the endometrial samples using the COBAS AMPLICOR™ (Roche Diagnostics, Branchburg, NJ, USA) polymerase chain reaction (PCR) identification system. Results: Chronic endometritis was the most common histologic finding (10/40, 25%) and occurred more often in women experiencing BTB (35% vs. 15%) (RR 1.62, CI 0.91–2.87). No patient with CE had CT infection of the endometrium or cervix. Conclusions: CT was not a cause of CE in this population of at-risk patients using DMPA. It is possible that CE in DMPA users reflects an inflammatory state, a function of an atrophic endometrium. This points to the possibility of nonsteroidal anti-inflammatory drugs as therapy for CE in this population rather than antimicrobials or hormonal medication. [Copyright &y& Elsevier]

Abstract: Objective: The objective of this study was to evaluate the effect of a continuous daily regimen of levonorgestrel (LNG) 90 μg/ethinyl estradiol (EE) 20 μg on endometrial histology. Methods: This was a substudy of a large phase 3 trial conducted in six sites in North America. Healthy and sexually active women aged between 18 and 49 years took LNG 90 μg/EE 20 μg daily for 1 year. Results from endometrial biopsies performed at pretreatment baseline and those after at least 6 months of treatment were compared. Results: Of the 146 participants, 93 had a baseline biopsy and completed at least six pill packs. Before treatment, 56 subjects (60%) had an endometrial biopsy with findings classified as “weakly proliferative or proliferative.” During the last on-therapy visit, 48 subjects (52%) had an endometrium categorized as “other,” which included primarily an inactive or benign endometrium (n=42). No hyperplasia or malignancy was observed during the study. Conclusion: The results of a 1-year continuous regimen of LNG 90 μg/EE 20 μg were shown to have a good endometrial safety profile. [Copyright &y& Elsevier]

Abstract: Introduction: The powdered dry root of Polygonum hydropiper is widely used by a certain ethnic group of women in Assam, India, for the prevention of undesired pregnancy. Method: In the present investigation, the estrogenic property of the crude root extract (CRE) of P. hydropiper [compared to estradiol-17β (E2), the reference drug] was tested in ovary-intact and ovariectomized (OVX) rats. The study was carried out by histological observations of ovarian follicles in an ovary-intact model and by histological observations of the endometrial epithelium in both OVX and ovary-intact female albino rats. Serial sections of the ovary and of the uterus were stained with routine hematoxylin–eosin and were observed under a microscope. Results: In the ovary-intact model, CRE induced follicular recruitment, while it promoted follicular atresia at a later stage. Many of the graafian follicles in the treated ovary showed pyknosis of the nuclei of granulosa and theca cells, as well as disparity in granulosa cell organization. In the uterine tissues of both ovary-intact and OVX rats, CRE induced hyperplasia in places of luminal epithelium and degeneration of endometrial glands. In OVX rats, the effect of CRE on uterine endometrium was corroborative with the effect of E2. Conclusions: Oral administration of the CRE of P. hydropiper significantly altered the histological structures of both ovary-intact and OVX rats. [Copyright &y& Elsevier]

Abstract: Objective: This descriptive study evaluated endometrial histology, microvascular density and caliber, and quantification of matrix metalloproteinase (MMP-3) expression in long-term users of the Nestorone® (NES)-releasing implant who presented or not endometrial breakthrough bleeding (BTB). Methods: Endometrial biopsies were obtained from 32 healthy women with unpredictable BTB. The quantitative analysis was performed only in 20 samples. Results: The mean duration of use of the implant among the 14 women with BTB was 19.6±1.0 months, and the other six women had used the implant for 17.7±2.3 months (mean±S.E.M.). Histological analysis of the endometrial tissue showed a predominance of progestogenic pattern followed by atrophic and proliferative endometrium in both groups. Mucosal breakdown and glandular pseudostratification were observed in half of the cases. Endometrial vascular density was 73.1±10.0 and 57.5±24.1 vessels/mm2, and maximum vessel diameter was 923.3±86.0 and 1038.0±404 μm (mean±S.E.M.) in the group with and without BTB, respectively, without significance, and the rate of cells expressing MMP-3×1000 counted stromal cells was 155.8±24.8 and 127.0±19.0 (mean±S.E.M.) in both groups, respectively, without significance. Conclusions: This study provides information about some endometrial aspects of women using NES in contraceptive implants. In addition, the endometrium was similar during long-term use of NES-releasing contraceptive implants in women with and without endometrial bleeding. [Copyright &y& Elsevier]

Abstract: We investigated the effects of NuvaRing on endometrial histology in a 2-year open-label, multicenter trial in 103 premenopausal women aged 18–35 years. Subjects received 26 cycles of treatment, each comprising 3 weeks of ring use followed by a 1-week ring-free period. Endometrial biopsies were taken at baseline, and at cycles 13 (month 12) and 26 (month 24). Normal biopsy results were obtained in all subjects after 24 months of NuvaRing treatment. Atrophic or inactive endometrium and secretory changes were present in the majority of the biopsies after 1 year and 2 years of treatment with the vaginal ring. It was concluded that long-term use of NuvaRing has no adverse effects on endometrial histology. [Copyright &y& Elsevier]

Abstract: This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats. [Copyright &y& Elsevier]

Abstract: Studies were undertaken to evaluate the influence of estrogen antagonist-cum anti-implantation agent, ormeloxifene, on 17β-hydroxydsteroid dehydrogenase (17β-HSD) activity and estrogen action in rat uterus during preimplantation period and to examine its ability to induce progesterone receptor (PR) in immature rat model. A group of female rats received orally a contraceptive dose of 1.25 mg/kg of ormeloxifene on Day 1 postcoitum (pc). Rats were sacrificed on Days 3, 4 and 5 pc, and uterine tissues were processed for enzymatic, estrogen receptor and estradiol (E2) estimations. Immature ovariectomized rats received ormeloxifene, subcutaneously for 3 days at various doses in the absence or presence of estradiol, and uterine PR levels were measured using 3H-R5020 as radioligand. Results revealed that ormeloxifene treatment caused a marked increase in enzyme activity of 17β-HSD on Days 3, 4 and 5 pc as compared to respective controls. Further, total uterine estrogen receptors as estimated by exchange assay showed a noticeable decrease on Days 4 (35%) and 5 (>80%) pc in ormeloxifene-treated groups. The results correlated well with a decrease in tissue E2 levels. In immature rats, ormeloxifene caused a dose-dependent increase in cytosolic PR levels; ormeloxifene given along with E2 (0.1 μg) for 3 days caused a significant reduction in concentration of PRs at 10 μg and higher doses. Ormeloxifene also induced 3H-progesterone (P) uptake by immature rat uterus. However, in the presence of E2, it significantly reduced 3H-P uptake. The in vitro competitive binding experiments did not reveal any displacement of 3H-R5020 either by ormeloxifene or by its hydroxy derivative from PR. The results suggest that in addition to its competitive antagonism at estrogen receptor level, ormeloxifene enhances the inactivation of intracellular E2 to estrone, a biologically less active form, thus declining estrogen receptor pool. Moreover, it causes indirect anti-progestational effects in the uterus by virtue of its anti-estrogenic profile rather than by blocking the PRs. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study is to investigate the safety and effectiveness of a short-scheme protocol of gemeprost for second trimester induction of abortion in women with previous uterine surgery. Study Design: Retrospective review of women who underwent second trimester medical termination of pregnancy (TOP) at our hospital in a 5-year period. A short regimen of gemeprost was used: over a 24-h period, 1 mg vaginal gemeprost was given every 3 h up to three doses after which, if abortion did not occur, another course at the same dosage schedule was administered up to 4 days. Induction failure was defined as women undelivered by 96 h. A homogeneous population was identified. Statistical analysis was performed with the χ 2 test or Fisher''s Exact Test for categorical data and t test for continuous variables. Results: Four hundred seventeen women underwent medical midtrimester TOP in the 5-year study period. Two hundred five patients were selected for this review, comparing 63 patients with scarred uterus to 142 women without uterine scars. There were no differences between the two groups in induction-to-abortion interval and number of pessaries given. The overall failure of induction rate was 1.5% and need for blood transfusion was 0.5%. No uterine rupture was reported. Conclusion: The regimen of gemeprost proposed seems to be as safe and effective in patients with uterine scars as in women with unscarred uteri with a very low incidence of complications. [Copyright &y& Elsevier]

Abstract: Levonorgestrel use in the levonorgestrel intrauterine device (LNG-IUS) induces vascular distension within the superficial layer of the endometrium and massive pseudodecidualization. With a computer-assisted image analysis system, we objectively measured the vascular bed in LNG-IUS users and compared it to the physiological endometrium. A study was undertaken on 25 women using LNG-IUS, in an outpatient procedure at the time of removal of the IUS and compared with 11 normally cycling women (control group). Suction curette specimens were obtained just after retrieval of the IUS, and immunohistochemistry was carried out with a specific marker of the endothelial cells (CD31). Number of vessels decreased in the LNG-IUS group to 60/mm2 versus 124/mm2 in the control group, and mean vessel area increased to 1255 μm2 versus 157 μm2, respectively, in the control group. The decrease in mean vascular density and the increase of mean vessel area in the LNG-IUS group, compared to the control group, were both highly significant (p&#60;.001). [Copyright &y& Elsevier]

Interception of pregnancy in its initial stage is an attractive and viable approach to contraception. A chemical agent, taken within the first few days of missed menses, intercepts the conception, which is expelled with menstrual flow. The main targets of such agents are the uterus, blastocyst and the growing trophoblasts, whose nutritional requirement is inhibited. Our previous work has identified several nonsteroidal chemical entities as pregnancy interceptives in rodents and infrahuman primates. However, none reached clinical stage due to their ineffectiveness by oral route. Nevertheless, parallel to these rationally designed synthetic compounds, a program was ongoing to identify natural product(s) that can be used as interceptives. We are reporting for the first time the detailed profile of emetine ditartrate, a compound whose pregnancy interceptive efficacy has been studied in mouse, rat, hamster, guinea pig and rabbit by oral and intravaginal routes of administration. By the oral route, the compound caused 100% resorption of the fetuses in rat, hamster and guinea pig at 6.0, 5.0 and 3.0 mg/kg, respectively, on administration during peri- and early postimplantation periods of pregnancy (depending upon the day of implantation in each species). By intravaginal route, the compound was administered once in the form of a vaginal pessary on the day of implantation in respective species; interception of pregnancy was not achieved completely in rat and hamster at doses four to five times the oral dose in multi-day schedule. However, in guinea pig and rabbit it was fully effective at 7.0 and 70.0 mg/animal, respectively. The compound was devoid of estrogenic, antiestrogenic and progestational activity but possessed mild antiprogestational activity at the high dose in vivo. In in vitro assay, however, it did not show any significant binding to estrogen and progesterone receptors. The mode of action of the compound was found to be mainly on the uterus and early embryos around implantation, possibly on the trophoblasts and endometrial cells at the attachment site. The absence of 100% efficacy in rat and hamster by intravaginal route, but not by oral route, is possibly due to poor absorption of the compound through the vagina in these species. The guinea pig and rabbit, therefore, seem the better species for evaluating the efficacy of the compound administered by the vaginal route. [Copyright &y& Elsevier]

This study evaluated the effectiveness and acute toxicity of DL111-IT combined with mifepristone (RU486) and misoprostol (MISO) on early pregnancy termination. In the pregnant rats experiments, the ED50 values of RU486 in two-drug combinations were 0.16 (combined with DL111-IT) and 0.40 (combined with MISO) mg · kg−1 · d−1, while in three-drug combination treatment group (DL111-IT 9.0 mg · kg−1 (

: BackgroundSpermicides containing nonoxynol-9 (N-9) may increase HIV transmission. In women, intravaginal N-9 is found in the uterus shortly after its insertion. Exposure of the female upper reproductive tract to N-9 may alter epithelial integrity, thereby increasing HIV transmission risk. Our goal was to characterize the histological effects of N-9 on uterine epithelium in an animal model.: MethodsFemale mice were exposed to intravaginal or intrauterine Advantage-S™ (N-9), Replens™, K-Y® jelly or water. After various exposure times, mice were sacrificed and stained uterine tissue sections were analyzed by a pathologist blinded to treatment.: ResultsIntravaginal and intrauterine N-9 administration resulted in disruption of uterine epithelium compared to Replens, K-Y jelly or water. N-9 caused rapid (within 10 min), focal, uterine epithelial sloughing and complete epithelial loss within 24 h. Epithelial regeneration began 48 h after exposure N-9 and was completely restored within 72 h; the new epithelial layer, however, was composed of cuboidal cells instead of normally present columnar cells. In addition, hemorrhage and necrosis were present are all time points examined.: ConclusionsOur results demonstrate for the first time that N-9 has a deleterious effect on uterine epithelium. Although these results were observed in a mouse model, similar disruption of the upper reproductive tract epithelium in women by N-9 may facilitate HIV infection and serve as an unrecognized portal of human HIV transmission. [Copyright &y& Elsevier]

The objective of the study was to evaluate, clinically and sonographically, the time required for the progestative effect of the levonorgestrel-releasing intrauterine system (IUS, Mirena) to be manifested. Doppler flow of the cervical branch and spiral artery of the uterine artery, as well as the endometrial width (up to day 10 of the cycle), were evaluated in 36 women carrying levonorgestrel-releasing IUS 1–2 months after insertion of the device compared to 4–6 months after insertion. The rate of intermenstrual bleeding was reduced from 44% during the first 2 months, to only 8% of women after 4–6 months of use. Complete cessation of menstrual bleeding occurred in 5% after 2 months and in 66% after 4–6 months following insertion. While there was no change in the Doppler flow in the cervical branch of the uterine artery between both groups, there was a significant reduction in the subendometrial flow in the spiral artery. This observation was reinforced by the demonstration of significant reduction in endometrial thickness in the following 4 months of use. The present study has demonstrated that the local progestative effect of the levonorgestrel-releasing IUS on the endometrium is already manifested within a period of 3 months and over after insertion. [Copyright &y& Elsevier]

Scarce data are available on the relation between the effectiveness of intrauterine device (IUD) and the gynecologic features of a woman. A nested case-control study was conducted to determine whether the uterine position and hysterometry affect the pregnancy rate of copper IUD. Seventy-one cases (pregnant women with IUD) and 284 matched controls (1:4) were included. Matching criteria were date of IUD insertion and duration of use. Data were analyzed by conditional logistic regression modeling that considered age, parity and copper surface of IUD as potential confounders. When cases were compared to nonpregnant controls with IUD, the results showed that uterine position and hysterometry were not associated with an increased risk of pregnancy. The findings suggest that the gynecological characteristics of the woman analyzed should not be a criterion for the selection of potential IUD users. [Copyright &y& Elsevier]

Insertion of Multiload Cu375 was studied in 16,159 women in a 10-year prospective observational cohort study in New Zealand. Of 17,468 insertions, about 9% were performed in nulliparous women.Problems fitting Multiload Cu375 (e.g., failed or difficult insertion) were experienced during approximately 2% of all insertions. The incidence of these was significantly higher in nulliparous women compared to parous women. Adverse reactions to insertion (e.g., pain, bleeding) occurred in 1.2% of all insertions, with nulliparous women experiencing significantly more adverse reactions than parous women.The insertions were performed by 1,700 different doctors in New Zealand with general practitioners performing 92% of these. Doctors who reported inserting over 100 devices in the study period experienced significantly less insertion problems than doctors who reported inserting less than 10 devices.This study suggests that insertion of Multiload Cu375 in a mixed community setting is associated with few inserting problems and adverse reactions to insertion. Risk factors identified for inserting problems included nulliparity and experience of the doctor inserting the intrauterine device. [Copyright &y& Elsevier]

Maytenus ilicifolia Mart. is used in Brazilian herbal medicine particularly for stomach disorders, but it is also used, as in other parts of South America, for fertility control. To verify its potential as an abortifacient, the lyophilized hydroalcoholic extract of its leaves was administered orally at a dose of 1000 mg/kg/day to mice between the first and third day of pregnancy (DOP), between the forth and sixth DOP, or between the seventh and ninth DOP. The extract caused a pre-implantation embryonic loss, but it did not have an effect on implantation or organogenesis. Morphological alterations of the reproductive system, not an embryotoxic effect, were not found. Estrogenic activity of the extract, exhibited by an uterotrophic effect, suggests that it may be interfering with the uterine receptivity to the embryo. [Copyright &y& Elsevier]

The expected trend in serum beta-human chorionic gonadotropin (β-hCG) following treatment of an undesired heterotopic pregnancy with uterine aspiration and systemic methotrexate is not known. Thus, monitoring for treatment success is challenging. We describe an undesired heterotopic pregnancy treated with aspiration and two-dose methotrexate and report the observed β-hCG trend., (Copyright © 2021 Elsevier Ltd. All rights reserved.)