Considerations on a new, frameless copper-releasing intrauterine system for intracesarean insertion and its future clinical significance: A review.

Family planning is a system for attaining the desired number of children and enabling a desired spacing between pregnancies. Family planning can be achieved through both the use of contraceptive methods and the treatment of infertility. A woman's ability to limit her pregnancy has a significant effect on her health.While family planning reduces the rate of unintented pregnancies, it also reduces the number of unsafe abortions. Contraception is an important component of family planning and reproductive health. Among various contraceptive methods, intrauterine devices (IUDs) are very popular because of some of the features of IUDs including being affordable, simplicity of insertion, long duration of action and reversibility. Modern, frameless, copper IUDs contain more copper and their copper content is contained in the solid tubular sleeves rather than in the wire which increases efficacy and lifespan. Immediate postpartum intrauterine device insertion (IPPI) during cesarean section can be considered in women who desire long acting, reversible contraception. Fertility returns instantly after removal of the device and pregnancy rate is not affected. IPPI is a very attractive method, especially for women who have undergone cesarean and require an interval of contraception before getting pregnant again. However, IPPI needs more clinical attention due to many aspects. The advantages remain including the prevention of unintended short interval pregnancies and, by providing an optimal timeframe for post-cesarean uterine recover, can reduce the incidence of the next cesarean delivery. With the publication of international IPPI studies, it will take a place in the range of globally available contraceptive methods, which in this author's opinion, it deserves.

Clinical experience with a novel anchored, frameless copper-releasing contraceptive device for intra-caesarean insertion.

OBJECTIVES: The primary objective of the study was to determine the expulsion rate of the newly developed frameless GyneFix Caesarean Section (Gyn-CS®) device, specifically developed to minimise expulsion when inserted immediately after delivery of the placenta during caesarean section. Secondary objectives included evaluation of side effects, patient's satisfaction with the method and continuation of use. METHODS: A prospective, non-randomised clinical trial was conducted at a single university hospital research centre in Istanbul, Turkey, with follow-up at 4-6 weeks and again at 3 months. The majority of participants (∼80%) were planned for elective caesarean delivery. RESULTS: The study analysed 100 Gyn-CS devices inserted immediately after delivery of the placenta in a group of multiparous women undergoing planned or emergency caesarean section. One expulsion occurred early in the study, which was subsequently attributed to improper anchoring of the device. No serious adverse events (e.g. pelvic inflammatory disease or perforation) were reported. At the last follow-up visit, at approximately 90 d, 89 Gyn-CS devices were still in place (one participant was lost to follow-up). CONCLUSION: The study confirms that intra-caesarean implantation of the newly designed frameless Gyn-CS to the uterine fundus is a simple procedure that has no timing restraints, high patient acceptance and minimal risk of expulsion and displacement, while affording all the contraceptive benefits of a conventional copper-releasing intrauterine device. In addition, by preventing a shortened interpregnancy interval, the Gyn-CS can promote proper healing of the laparotomy wound. As insertion is easy, safe and quick, the Gyn-CS could significantly increase the use of immediate postplacental delivery intrauterine contraception, thus serving to reduce the number of unintended follow-on pregnancies.

Comparison of expulsions following intracesarean placement of an innovative frameless copper-releasing IUD (Gyn-CS®) versus the TCu380A: A randomized trial.

OBJECTIVE: The intent of this study (primary outcome measure) is to assess the expulsion rate of a newly developed copper releasing frameless intrauterine IUD GyneFix® Cesarean Section (Gyn-CS®) at 3 months' follow-up, compared to the TCu-380A IUD, inserted immediately postplacental expulsion following cesarean section delivery. STUDY DESIGN: This is a randomized trial from one hospital research center in Istanbul, Turkey. Eligible pregnant women, the majority undergoing elective cesarean delivery (n=106), and the remaining emergency cesarean section cases (n=34), received intracesarean insertion of Gyn-CS or TCu380A insertion. Follow-up ended with a 3 month-visit. The Zeynep Kamil University Hospital Ethics Committee approved this study. RESULTS: The study explores the retention of 140 insertions, 70 Gyn-CS and 70 TCu380A. There were two follow-up visits after discharge from hospital at 6 weeks and 3 months. A single Gyn-CS expulsion occurred after approximately 6 weeks likely a consequence of improper anchoring. Expulsion was more common in the TCu380 A IUD group (11.4% vs 1.4%, p=.039). There were 4 removals for medical reasons in the Gyn-CS patients and 4 in the TCu380A patients, respectively, with 4 non-medical removals occurred, 2 in each group. No serious adverse events (e.g., PID, perforation) were reported. At the study conclusion of 3 months, 61 Gyn-CS (88%) and 54 TCu380A (79%) IUDs remain in place. CONCLUSION: This immediate postplacental study in cesarean section patients suggests that the anchoring technique employed resulted in the excellent retention of Gyn-CS. Insertion was easy, safe and quick requiring minimal physician training. The possibility of direct visualization of the anchor by ultrasound at insertion and follow-up allows the surgeon to verify the position of the IUD serving to enhance provider and patient confidence and assurance. IMPLICATIONS: The frameless anchored intrauterine IUD is effective in minimizing displacement and expulsion. The results of this study suggest that the Gyn-CS IUD is appropriate for wider intracesarean use.

Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management.

Globally, endometrial cancer is the sixth leading cause of female cancer-related deaths. Non-atypical endometrial hyperplasia (EH), has a lifetime progression rate to endometrial cancer ranging from less than 5%, if simple without atypia, to 40%, if complex with atypia. Site specific, long-acting intrauterine devices (IUDs) provide fertility sparing, progestin-based EH medical management. It is unclear which IUD is most beneficial, or if progesterone sensitizing metformin offers improved outcomes. For resolution, PubMed searches for "Mirena" or "Metformin," "treatment," "endometrial hyperplasia," or "stage 1 endometrial cancer," were performed, yielding 33 articles. Of these, 19 articles were included. The 60 mg high-dose frameless IUD/20 mcg levonorgestrel has achieved sustained regression of Grade 3 endometrial intraepithelial neoplasia for 14 years. Case series on early stage endometrial cancer (EC) treatment with IUDs have 75% or greater regression rates. For simple through complex EH with atypia, the 52 mg-IUD/10-20 mcg-LNG-14t has achieved 100% complete regression in 6-months. Clearly, IUDs have an outcome advantage over oral progestins. However, studies on metformin for EH, and of progestins or metformin for early stage EC management are underpowered, with inadequate dose ranges to achieve significant differences in, or optimal outcomes for, the treatment modalities. Therefore, outcomes from the feMMe trial for the 52 mg-IUD/10-20 mcg-LNG-14t and metformin will fill a gap in the literature.

Current status of frameless anchored IUD for immediate intracesarean insertion.

Immediate postpartum intrauterine device (IUD) insertion deserves great attention as it can provide immediate, timely and convenient contraception plus the added benefit of preventing repeat unintended pregnancies. Although women post vaginal delivery can benefit from immediate post-placenta contraception, women undergoing Cesarean section clearly need contraception, as an inter-delivery interval shorter than 18 months places them at a high risk for uterine rupture. The main drawback of currently available framed IUD devices for immediate postpartum insertion of an IUD is their high expulsion and displacement rates when inserted immediately postpartum after both vaginal and Cesarean delivery. Current research suggests that a brief window of opportunity exists of 10 minutes for insertion of conventional IUDs after which time expulsion rates both immediately and over time are greatly enhanced. This paper summarizes the current research conducted to overcome the expulsion problems associated with conventional T-shaped devices as well as through the use of an anchored frameless device. In the 1970s and 1980s, attempts were made to solve the expulsion problem by modifying existing devices, such as adding absorbable sutures (Delta-T) or additional appendages. These attempts proved to be clinically unsuccessful as the catgut suture added to the transverse arms did not provide sufficient resistance to prevent downward displacement and expulsion. An anchoring technique to suspend a copper IUD to the fundus of the uterus was developed in Belgium in the 1980s and has been the subject of extensive ongoing clinical research since 1985. Recently the frameless copper releasing anchor IUD, GyneFix, has been tested for postplacental insertion. Initially, the anchor was modified by the inclusion of a biodegradable cone which was added below the anchoring knot. Clinical studies confirmed the adequacy of this approach suggesting that it was technically possible to anchor an IUD immediately following Cesarean section as well as after vaginal delivery with minimal incidence of expulsion. However, it was found that removal of the IUD was difficult in a number of women who requested early removal, due to the slow disintegration time of the cone. Based on these prior experiences, a new approach for anchoring of a frameless IUD immediately after delivery of the placenta was invented and developed specifically for use immediately post-Cesarean delivery. Beyond providing convenient and timely contraception the intended use allows a woman adequate time to recover from both the surgery and the burden of childbirth, while ensuring adequate future contraception. It is anticipated that it will also have an added benefit of allowing a greater number of women to have follow-on vaginal deliveries. The anchoring procedure is conducted under direct vision. It can be performed immediately after placental removal without the burden of timing restraints. It consists of the precise placement of the anchor of the frameless IUD immediately below the serosa of the uterus, followed by fixing the anchoring knot in place with a very thin absorbable suture. Early stage studies have confirmed the suitability and ease of use of this approach with additional clinical trials currently being conducted. The anchoring technique is easy, quick, safe and effective with no expulsions at 12 months. The method is considered a major advance, suitable for general use due to its simplicity requiring limited training.

Intrauterine systems: a frameless future?

INTRODUCTION: Intrauterine devices (IUD) are viewed as important contraceptive methodologies to prevent unintended pregnancy. AREAS COVERED: This expert opinion examines the place of frameless devices for use in young women in order to minimize side effect, improve patient comfort and maximize continuation of use to help reduce unintended pregnancies. EXPERT OPINION: Frameless designed IUDs have the ability to be used in both small and large uterine cavities of varied shapes and can significantly reduce abnormal bleeding, pain, embedment and expulsion and likely account for higher continuation rates than that seen with framed IUDs.

Intrauterine device quo vadis? Why intrauterine device use should be revisited particularly in nulliparous women?

BACKGROUND: Long-acting reversible contraceptive (LARC) methods, including intrauterine devices (IUDs) and the contraceptive implant, are considered the best methods for preventing unintended pregnancies, rapid repeat pregnancy, and abortion in young women. An opinion paper of 2012 by the American College of Obstetricians and Gynecologists recommends Mirena and Paragard for use in nulliparous and adolescent women. However, these IUDs are not designed for young women and are not optimal as they often lead to early discontinuation. OBJECTIVE: This article was written with the objective to respond to the urgent need to improve intrauterine contraception as it is likely that the objectives of LARC will not be met without significant improvement of IUD design. Anatomical variations in size and shape of the uterus are not sufficiently considered, producing harm and suffering, which often lead to early removal of the IUD. PROPOSED PROBLEM SOLVING: The article describes why IUDs should be revisited to meet the challenge of LARC and proposes how to solve these problems. The opinion statement presented here may be considered provocative but is based on hundreds of women with IUD problems who consult or are referred to the practices of the authors of this article due to the disproportion between the IUD and their small uterine cavity. The solution is simple but requires a revision of the current design of IUDs. One-dimensional (longitudinal) IUDs are likely to be the first option. Framed devices with shortened transverse arm and IUDs which adapt to the width of the given uterus are viewed as second best. CONCLUSION: One of the reasons of the high unintended pregnancy rate in the USA may be the paucity of suitable IUDs. Also, the legal climate in the USA seems to be a problem for developers as many lawsuits have recently been reported. Clinical studies conducted in young nulliparous and adolescent women suggest that IUDs that fit well in the uterine cavity, like a shoe, result in better tolerance, less side effects, and last but not least, higher use continuation rates.

Expulsion and continuation rates after postabortion insertion of framed IUDs versus frameless IUDs - review of the literature.

BACKGROUND: Early intrauterine device (IUD) discontinuation after insertion immediately following aspiration abortion or after early medical abortion occurs as a consequence of expulsion of the IUD or removal due to side effects. These are often the consequence of the uterine forces impacting on the IUD due to spatial discrepancy with the uterine cavity causing pain, abnormal bleeding, and eventually, removal of the IUD. These women are candidates for repeat pregnancy as they often select less-effective methods or no contraception at all. Repeat abortion could be reduced by giving attention to these factors. STUDY DESIGN: In order to have an indication on the magnitude of the problem of IUD expulsion or discontinuation, we searched the MEDLINE database for clinical trials, randomized controlled trials, and prospective observational studies related to immediate postaspiration termination of pregnancy (TOP) and early medical abortion IUD insertion studies that reported IUD expulsion and IUD continuation rates. RESULTS: The search identified 17 clinical trials that were suitable based on the data they presented. The majority concerned T-shape IUDs, inserted immediately following surgical (aspiration) pregnancy termination. Two studies were conducted after medical TOP, and four studies were conducted with the frameless IUD inserted after surgical (vacuum aspiration) TOP. The results showed expulsion rates between 0.8% and 17.3% at 8 weeks, up to 5 years after insertion, respectively. In four studies with the frameless IUD, totaling 553 insertions, the expulsion rate was 0.0% in three of them. Follow-up in the latter studies varied between 5 weeks and 54 months. Reported continuation rates with conventional (framed) IUDs were between 33.8% and 80% at 1 year for studies providing 1 year rates and between 68% and 94.1% for studies reporting continuation rates at 6 months. Studies utilizing frameless IUDs reported 1 year continuation rate over 95%. CONCLUSION: Frameless IUDs, due to their attachment to the uterine fundus, appear to be better retained by the postabortal uterus when compared with conventional framed IUDs. The absence of a frame ensures compatibility with uterine cavity anatomical dimensions, and may therefore result in improved acceptability and continuation rates in comparison with framed IUDs. Both these characteristics of the frameless IUD could help reduce the number of repeat unwanted pregnancies and subsequent abortions in some cases.

Assessment of copper corrosion from frameless copper IUDs after long-term in utero residence.

OBJECTIVE: To assess the site-specific corrosive behavior of the frameless intrauterine device (IUD) following long-term exposure to the uterine environment. STUDY DESIGN: A qualitative and morphological study using X-ray diffraction (XRD) and scanning electron microscopy (SEM). RESULTS: Three GyneFix® IUDs that were in site up to 150 months were examined. In utero corroded copper sleeves were divided into 10 different groups based on their shape (U or O), orientation (inside or outside) and in utero residence time. XRD indicated the presence of solely cuprite (Cu2O) as corrosion product on both the inside and the outside of the copper sleeves, regardless of their shape. These results were confirmed by backscattered electron micrographs recorded on the inside, the outside and the cross-section of the IUD sleeve. SEM results suggest that shape and orientation slightly affect the corrosion rate. CONCLUSION: The apparent copper loss from both sides of GyneFix copper tubes proves that both sides are a potential copper source and therefore justifies the design of GyneFix IUD. This could be beneficial for women as the IUD could be reduced in size and therefore better tolerated. The impact on bleeding could also be minimized. IMPLICATION STATEMENT: Release of copper ions from both sides of the copper tubes of the frameless GyneFix® IUD allows the IUD to be reduced in size, contributing to better toleration. The impact on menstrual bleeding is also minimized by a smaller size of the foreign body.