Survival of isolated human preantral follicles after vitrification: Analyses of morphology and Fas ligand and caspase-3 mRNA expression.

Objective: This study aimed to examine the effect of vitrification on apoptosis and survival in human preantral follicles after thawing.

Methods: This experimental study was conducted at an acute tertiary care hospital from March 2012 to April 2013. Ovaries were sliced into 5×5×1-mm pieces and divided into the following three groups: preantral follicle isolation, ovarian tissue vitrification-warming followed by follicle isolation, and immunohistochemistry of fresh ovarian tissue.

Coexpression of fractalkine and its receptor in normal human endometrium and in endometrium from users of progestin-only contraception supports a role for fractalkine in leukocyte recruitment and endometrial remodeling.

Leukocytes are critical mediators of endometrial remodeling, but the mechanisms by which leukocyte subpopulations enter the uterus are currently unknown. Endometrial leukocytes have no genomic progesterone receptors; thus, we hypothesized that leukocyte migration is induced indirectly by progesterone-regulated chemokines. Fractalkine (CX3CL1), a chemotactic membrane-bound adhesion factor, and its receptor (CX3CR1) were assessed by immunohistochemistry in endometrial samples across the menstrual cycle, in early pregnancy, and in women using progestin-only contraceptives.

The 'frameless' intrauterine system for long-term, reversible contraception: a review of 15 years of clinical experience.

Aim: The development of the 'frameless' intrauterine system (IUS) is a response to the growing need to develop high-performing, long-acting, reversible, and acceptable contraceptives with a high continuation of use.

Methods: This is a review of 15 years of clinical experience in randomized controlled and non-randomized clinical trials.

Results: The IUS has a similar failure rate as the TCu380A Intrauterine device (IUD), considered the 'golden standard' IUD, which is attributed to the optimal target delivery of the copper ions in the upper part of the uterine cavity.

Long-acting progestogens.

Steroids can be administered in at least five different ways: injectables; hormone-releasing intra-uterine devices (IUDs); implants; vaginal rings; and pills. Progestogens which are synthetic steroids, are used as the main bioactive substances. Different progestogens are effective for different periods of time.

Decreased tissue inhibitor of metalloproteinase in the endometrium of women using depot medroxyprogesterone acetate: a role for altered endometrial matrix metalloproteinase/tissue inhibitor of metalloproteinase balance in the pathogenesis of abnormal uterine bleeding?

Background: Abnormal uterine bleeding is commonly associated with progestin-only contraceptives, including depot medroxyprogesterone acetate (DMPA), and remains the main reason why these agents are discontinued. Matrix metalloproteinases (MMP), enzymes which degrade specific extracellular matrix components, and leukocytes are implicated in menstruation. Alteration in endometrial MMP-9 and leukocytes has been described in users of other progestin-only contraceptives, suggesting a potential role in the pathogenesis of abnormal uterine bleeding.

Endometrial expression of glycodelin in women with levonorgestrel-releasing subdermal implants.

Objective: To determine whether subdermal levonorgestrel implants induce endometrial expression of glycodelin.

Design: Cross-sectional, blinded study.

Setting: University clinic.

Expression of the chemokines, monocyte chemotactic protein (MCP)-1 and MCP-2 in endometrium of normal women and Norplant users, does not support a central role in macrophage infiltration into endometrium.

The endometrium contains many leukocytes, including macrophages, the numbers varying with the time of the menstrual cycle and being maximal peri-menstrually. The long-acting progestogenic contraceptive Norplant, has a high rate of discontinuation due to uterine bleeding; this is associated with large numbers of endometrial macrophages. Monocyte chemotactic proteins (MCP) act to recruit and activate monocytes into sites of inflammation.

Inhibin and activin subunits are differentially expressed in endometrial cells and leukocytes during the menstrual cycle, in early pregnancy and in women using progestin-only contraception.

Inhibins and activins are dimeric hormones which share common subunits and which have diverse endocrine and paracrine roles in regulating reproductive function. Endometrial expression of inhibin alpha, ssA and ssB subunits was examined by immunohistochemistry and in-situ hybridization, across the menstrual cycle and in early pregnancy. All three subunits were found to be expressed in endometrium, primarily by glandular epithelium in the early stages of the cycle.

Endometrial epithelial integrity and subepithelial reticular fibre expression in progestin contraceptive acceptors.

Long-acting progestin contraceptives have been available in many countries for a number of years with a large number of women now using them. Although some improvements in delivery systems have been made, the major problem with progestin-only contraceptives remains unpredictable endometrial breakthrough bleeding (BTB), which is responsible for more than 50% of drop-outs from this form of contraception. Using hysteroscopy, endometrial petechiae and ecchymoses are a common finding among Norplant users, although these features do not always correlate with BTB.

Bcl-2, Fas and caspase 3 expression in endometrium from levonorgestrel implant users with and without breakthrough bleeding.

Women using the progestin-only contraceptive Norplant often suffer from unpredictable bouts of breakthrough bleeding, which usually occurs from a thin atrophic endometrium. The role of cellular apoptosis in the endometrial response to Norplant has not been investigated. The aim of the present study was to use immunohistochemistry to produce semi-quantitative scores for expression of the apoptosis-related proteins Bcl-2, Fas and caspase 3 in endometrium from 16 controls and 42 women using Norplant with minimal or major breakthrough bleeding problems.

Perivascular smooth muscle alpha-actin is reduced in the endometrium of women with progestin-only contraceptive breakthrough bleeding.

It has been shown that the endometrium of women using progestin-only contraceptives has increased vascular fragility, although the structural basis for this weakness is unknown, as is its role in breakthrough bleeding (BTB). Perivascular cells such as pericytes and vascular smooth muscle cells surround capillaries during the maturation process following angiogenesis, and act to strengthen and stabilize the vessels. The aim of the present study was to quantify endometrial perivascular smooth muscle alpha-actin (alphaSMA) expression in women using Norplant with and without BTB problems, and compare it to controls.

Oxidative stress, vitamin E and progestin breakthrough bleeding.

Endometrial bleeding problems can be the major reason for discontinuing progestin-only contraception. In this study the endometrial angiogenic response in Norplant users was found to be lower than in women with normal menstrual cycles. These disturbances in angiogenic response may be caused by oxidant-antioxidant imbalance in the endometrium.

Benefits of vitamin E supplementation to Norplant users--in vitro and in vivo studies.

Norplant subcutaneous implantation is a contraceptive method used in Indonesia. Endometrial bleeding is one major reason to discontinue the use of Norplant. Angiogenic response in the endometrium of Norplant users was found to be lower than in women with normal menstrual cycle.

The effects of Implanon on lipid metabolism in comparison with Norplant.

This open, randomized study was intended to assess the effects of the new single-rod contraceptive implant (Implanon) containing etonogestrel on lipid metabolism in Indonesian women, in comparison with the six-rod implant Norplant, containing levonorgestrel. The effects of both products were compared with a control group using an intrauterine device (IUD) over a 3-year period. A total of 135 healthy volunteers of childbearing potential, aged 22 to 41 years, were enrolled in Jakarta, Indonesia.

Matrix metalloproteinase-1 and -3 and mast cells are present in the endometrium of women using progestin-only contraceptives.

Progestin-only contraceptives are associated with menstrual bleeding disturbances; a major reason why these agents are discontinued. The pathogenesis of such abnormal uterine bleeding associated with progestin-only contraceptives remains ill-defined. Matrix metalloproteinases (MMP)s and mast cells (MC)s are postulated to be involved in endometrial breakdown observed in normal menstruation.

A pilot efficacy study with a single-rod contraceptive implant (Implanon) in 200 Indonesian women treated for < or = 4 years.

In this 4-year open-label, noncomparative, single-center pilot efficacy study, the contraceptive efficacy, safety, bleeding pattern and acceptability of Implanon was studied in 200 sexually active women of proven fertility in Indonesia. All subjects received the single-rod subdermal implant Implanon, which contains 68 mg etonogestrel (3-keto-desogestrel), with an initial release rate of 67 micrograms etonogestrel/day. Contraceptive efficacy was analyzed by calculation of the pregnancy rate, bleeding patterns were determined by the 90-day reference period method, and acceptability by the discontinuation rate.

Endometrial breakdown in women using Norplant is associated with migratory cells expressing matrix metalloproteinase-9 (gelatinase B).

Norplant, subdermally implanted slow-release levonorgestrel, is an effective and widely used contraceptive agent but has a high rate of discontinuation due to unacceptable abnormal uterine bleeding. Matrix metalloproteinases (MMPs) are expressed in normal cycling endometrium and are postulated to be responsible for the tissue breakdown at menstruation. We have compared the immunolocalization of MMP-9 and migratory cells in endometrium from Indonesian women using Norplant with normal controls.

An integrated analysis of vaginal bleeding patterns in clinical trials of Implanon.

The vaginal bleeding patterns observed during the use of the single-rod progestin-only implant, Implanon, compared with those seen during the use of the six-capsule implant, Norplant, have been analyzed. The acceptability of these bleeding patterns was also assessed. An integrated analysis of 13 different trials was done, studying reference periods (RP) of 90 days.

The effects of levonorgestrel implants on vascular endothelial growth factor expression in the endometrium.

Vascular endothelial growth factor (VEGF) expression and the microvascular density of the endometrium were studied in Norplant users and normal controls, using immunohistochemistry on formalin-fixed paraffin-embedded endometrial sections. The VEGF staining index was quantified using computerized image analysis. The VEGF staining index between stages of the menstrual cycle and between normal and Norplant endometria were compared.

Norplant consensus statement and background review.

This review has highlighted the attributes of a very important new method of contraception. The signatories to this document agree that, with the provision of appropriate information and instruction for the user, Norplant is a good contraceptive choice to be made available worldwide in family planning programs that have the resources for appropriate training and counseling. The signatories to this document are acting in their own personal capacity and not as representatives of any particular organization.

Levonorgestrel-releasing intrauterine device-wearing women express contraceptive glycodelin A in endometrium during midcycle: another contraceptive mechanism?

Intrauterine devices (IUDs) exert contraceptive action by interfering with sperm transport, ovum development, fertilization and implantation. Glycodelin A (GdA) is a uterine glycoprotein that has local contraceptive activity by inhibiting sperm-egg binding. GdA is normally absent from endometrium during the fertile midcycle and it is not expressed until the fifth postovulatory day.

Training for Norplant implant removal: assessment of learning curves and competency.

Objective: To determine the learning curves and rapidity with which clinicians become competent in implant removal using two Norplant removal techniques.

Methods: Twenty-four physicians, none of whom were experienced in the use of Norplant implants, were randomly assigned to learn either the "U" removal technique or the standard technique. The physicians in the two groups received identical training in all other respects.

Expression of progesterone receptor mRNA in the endometrium during the normal menstrual cycle and in Norplant users.

The expression of endometrial progesterone receptor mRNA during the human menstrual cycle and in Norplant users was studied using digoxigenin-labelled ribonucleic probes for in-situ hybridization on 6 microns paraffin embedded endometrial sections. The staining intensity was scored blind semi-quantitatively. Blood ovarian steroid concentrations were measured in Norplant users.