Menstrual Induction Research Articles

Survey of changes in ovarian and uterine artery blood flow and indexes by transvaginal Doppler sonography in POI patients and effect of acupuncture on their fertility

Background: Primary ovarian insufficiency (POI) is a common cause of infertility and usually defined by the triad of amenorrhea, estrogen deficiency, and elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in women < 40 years of age. The aim of the present study was to investigate the relationship between uterine and ovarian blood flow with acupuncture and fertility ratio in patients of the Firoozgar Hospital Infertility Clinic. Methods: Twenty-nine patients with POI were included in this clinical trial. FSH, LH, estradiol (E2), and anti-Müllerian hormone (AMH) levels were measured. Patients with Turner syndrome were identified and excluded from the study. Selected patients were evaluated using transvaginal color Doppler sonography used to measure ovarian volume, endometrial thickness, flow rates, and uterine and ovarian artery indexes. Patients were treated with acupuncture twice a week for 5 weeks. After the end of treatment, hormonal assays and an ultrasound examination were repeated to check the changes. Results: Indexes of the uterine arteries (Resistance Index, Pulsatility Index) before versus after the intervention were significantly different (P < 0.00) and uterine vascularity increased after treatment in 22 patients (75.8%). LH and FSH hormone levels were significantly decreased after the intervention (P < 0.00), while AMH and E2 levels were significantly increased after treatment (P < 0.00). The post-intervention right ovarian reserve was significantly increased (P = 0.02), whereas there was no significant difference in left ovarian reserve before vs. after treatment (P = 0.39). Spontaneous menstruation was detected after acupuncture in 16 patients. Conclusions: Our study demonstrated changes in vascularity, hormone levels, menopausal symptoms, and menstrual induction in patients after acupuncture intervention. Keywords: POI, acupuncture, arterial indexes.

Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model

Ethnopharmacological relevanceChickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS). Aim of the studyIn this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model. Materials and methodsThirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured. ResultsIn all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS. ConclusionsIn the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.

The current status of 492 adult women with Turner syndrome: a questionnaire survey by the Foundation for Growth Science

Current status and its background of Adult Turner Syndrome (TS) are not clarified well. Via a questionnaire survey of 492 adult women with TS, this study investigated the association between menstruation, Kaufmann therapy (menstrual induction therapy), social status (education, employment & marriage), complications, transition from pediatric to adult care, and sex chromosome karyotype using statistical methods. Spontaneous menarche occurred in 22.0% and more frequently among patients with the 45,X/46,XX karyotype. Over 60% of these subjects, menstruation did not persist regularly. Kauffmann therapy was performed in 69.4%; the most common formulation was a conjugated estrogen and progesterone combination. Marriage and higher education advancement rates were low in adults with TS, whereas their employment rate was similar to that of the age-matched general female population. Patients receiving Kauffmann therapy had higher complication rates, greater education length, and higher employment rates. The higher-education advancement rate was observed among patients with 45,X/46,X,Xi and 46,X,Xi karyotypes. Transition from pediatrician to adult specialist was not smooth, subjects were treated in pediatric departments (60.7%), gynecological department (21.4%), internal medicine departments (13.3%), and others. While reason is not clear, the largest number of TS patients are treated in general pediatrics and the percentage of receiving Kauffmann therapy and having complication were significantly lower than in pediatric and adult department of endocrinology (& metabolism). This Study revealed many novel findings of adult TS.

Profile of Women with Late Menstrual Period

Objective: To know the profile of women with late menstrual period in Raden Saleh Clinic Jakarta in 2008 - 2011.
 
 Method: This was a descriptive study with 400 samples from medical records, choosen by random sampling. The data of age, education, occupation, marital status, residence, religion, parity, age of the youngest kid, cause of pregnancy, attempt to abort, referral, reason to end pregnancy, and contraceptive method post menstrual induction were collected.
 
 Result: The majority of women who underwent menstrual induction were 18 - 35 years old (57.25%), followed by women aged more than 35 years old (40.5%) and below 18 years old (2.25%). Most women were graduated from middle school (51.25%), unemployed (65.25%), and married (90.8%). They mostly came from Jakarta and
 satellite cities such as Depok, Bogor, Tangerang, and Bekasi, which accounted for 88% clients. Most of them have two children (32.3%) with the youngest kid aged more than 12 months old (60%). The causes of pregnancy were neglecting to use contraception (87.5%), failure of contraception (12%), and sexual assault (0.5%). As much as 44% of the clients had tried to end the pregnancy before they came to Raden Saleh Clinic and 87.5% of all 400 women came without referral. The most common reason was having had enough children in 74% of the women to end the pregnancy, followed by 12.25% of clients who wanted to pursue higher education. After
 treated by menstrual induction, 75.8% of them used IUD as contraception.
 
 Conclusion: Our data showed that mean age of women who were underwent menstrual induction is 32.94 ± 0.35 years old and the main reason to do menstrual induction in this research is the consideration of having enough children.
 
 [Indones J Obstet Gynecol 2013; 37-1: 41-5]
 
 Keywords: age, contraception, late menstrual period, menstrual induction

Intratumoral Hemorrhage of Mammary Phyllodes Tumor After Menstrual Induction: A Puzzling Presentation

Mammary phyllodes tumor is an uncommon stromal-epithelial neoplasm with a reported incidence of 0.3% to 0.5% of female breast tumors. Sudden, rapid growth of a mammary phyllodes tumor with intratumoral hemorrhage was noted in a 45-year-old woman after menstrual induction with progesterone and norethindrone acetate. This case is presented here to highlight the possibility of such an onset of phyllodes tumor in order to facilitate its prompt diagnosis. A 45-year-old woman suffered from missed periods for 2 months and received progesterone for menstrual induction. After treatment, rapid enlargement of her left breast was noted. Tracing the history of the patient, we found that she had already felt an about 3 cm painless lump in her left breast 5 months before this episode. Sonography of the left breast showed a large cystic lesion with some echogenic content and about 150 mL of old blood was obtained by aspiration. Surprisingly, follow-up breast sonography 3 weeks later revealed a large irregular solid mass and a small amount of peripheral cystic content with markedly increased vascularity. Surgery was suggested. A large encapsulated mass consisting of heterogeneous yellow soft tissue and a cystic component measuring 10 x 8 cm was totally excised. Microscopically, the sections revealed branching and cystically dilated glands lined by cuboidal to columnar epithelial cells in a myxoid hypercellular fibroblastic stroma with hyperchromatic nuclei and frequent mitotic figures. The final histological diagnosis was malignant phyllodes tumor. Progesterone for menstrual induction may cause rapid growth of a phyllodes tumor with resultant internal hemorrhage. Only with the awareness of this entity can a prompt diagnosis be made and optimal treatment be given.

Summary of evidence and research needs on the use of mifepristone in fertility regulation: consensus from the conference

The conference on the use of mifepristone to reduce unwanted pregnancy, sponsored by the World Health Organization, Concept Foundation and the Rockefeller Foundation, took place in Bellagio, Italy, between 24 and 28 September 2001. The objective of the conference was to review the scientific information and to evaluate the use of mifepristone for emergency contraception, luteal contraception and menstrual induction. Mifepristone is highly effective for emergency contraception but its advantages and disadvantages in comparison with levonorgestrel need to be further studied. Data indicate that mifepristone alone or in combination with misoprostol has potential for occasional use for women seeking help following repeated unprotected intercourse and/or when the interval between intercourse and treatment is more then 120 h. Administration of mifepristone immediately after ovulation seems to be an effective contraceptive method. However, before it can be used commonly, there is a need for a simple and inexpensive method to identify the right time in the cycle. Once-a-month treatment with mifepristone and misoprostol at the expected time of menstruation is not a practical method due to bleeding irregularities and timing of treatment. Menstrual induction with mifepristone and a suitable prostaglandin analogue is highly effective. A randomized comparison with manual vacuum aspiration is, however, needed before it can be recommended for routine use.

Menstrual induction with mifepristone and misoprostol

Menstrual induction refers to early uterine evacuation without laboratory confirmation of pregnancy in women with delayed menses. Mechanical aspiration is the method used in many countries but, as suggested by a pilot study, mifepristone followed by a prostaglandin analogue could also be effective. We launched the present study to evaluate the efficacy and side effects of 150 mg of mifepristone, followed 2 days later by 0.4 mg misoprostol vaginally, for menstrual induction among women with a menstrual delay of up to 7 days. The outcome of treatment was uterine evacuation, which could mean menstruation or termination of early pregnancy. A total of 720 women were recruited. The mean delay of menstruation at recruitment was 4.9 (SD = 1.7) days. Retrospective analysis of human chorionic gonadotropin from serum samples taken at admission showed that 492 (68.3%) women were pregnant at admission, and 228 (31.7%) women had delayed menstruation without pregnancy. One nonpregnant woman was lost to follow-up. Bleeding was induced in 479 (97.4%) pregnant women and in 222 (97.8%) nonpregnant women. Among the pregnant women, 455 (92.5%) had complete abortion, 12 (2.4%) had incomplete abortion and pregnancy continued in 25 (5.1%) women, including one ectopic pregnancy. Side effects were mild and uncommon. We conclude that 95.8% of the women treated had the expected outcome. Further research is needed to compare the efficacy, safety and acceptability of the medical regimen to vacuum aspiration. A rather high continuing pregnancy rate in this study is a concern.

The possibility of using mifepristone for menstrual induction

Menstrual induction is a variant of suction aspiration that was originally defined to be performed in women with a menstrual delay of up to 2–3 weeks without knowing if the women is pregnant or not. Prerequisites for a pharmacological method for menstrual induction are a high efficacy to induce a bleeding in nonpregnant women and an expulsion of the pregnancy in pregnant women. Treatment with prostaglandins, specifically intramuscular sulprostone, can be as effective as suction aspiration for menstrual induction. However, the administration of prostaglandin in therapeutically effective doses was associated with a high frequency of gastrointestinal side effects and, to a lesser extent, of strong abdominal pain, which limited their routine use. More recent studies indicate that mifepristone in combination with either misoprostol or gemeprost is a more promising alternative. Further studies to identify the best treatment schedule are, however, needed, as is a randomized comparison with suction aspiration before a pharmaceutical method can be recommended.

Mifepristone: a novel estrogen-free daily contraceptive pill

When the first synthetic progesterone antagonist (mifepristone) was synthesized over 20 years ago, it was clear that it had a potential as an antifertility agent. Research into the use of antiprogestogens for contraception have concentrated on three general approaches: (1) inhibition of ovulation, (2) inhibition of implantation and (3) disruption of implantation or “menstrual induction”. The effect of mifepristone on the ovarian and endometrial cycle depends on dose, timing and frequency of administration. Doses of 10 mg per day or more suppress follicular development and estradiol levels. Ovulatory cycles are maintained in the dose of less than 2 mg although there is increased variability in cycle length. The endometrium shows some minor asynchronous changes, although these are not sufficient to prevent pregnancy. We have chosen to investigate daily doses between 2 and 5 mg which inhibit ovulation and menstruation in over 90% of cycles while still maintaining follicular development and levels of estradiol within the range found during the follicular phase. The endometrium shows proliferative or cystic changes lined by a layer of inactive glandular epithelium set in densely packed stroma. There is, however, an absence of proliferative activity as reflected by a reduced mitotic index and Ki67 staining. These unusual histological appearances are associated with downregulation of PR but a massive upregulation of AR in particularly glandular epithelium. The antiproliferative effect of mifepristone is reassuring suggesting that the risk of atypical hyperplasia due to the effect of prolonged exposure to estrogen unopposed by progesterone is low. In a pilot study, there were no pregnancies in 200 months of exposure in 50 women who used this method as their sole method of contraception. Daily mifepristone could provide a novel contraceptive method which should be devoid of the risks associated with estrogen containing combined oral contraceptive (COC), e.g. venous thromboembolism. The health benefits of avoiding the morbidity associated with menstruation are considerable. Recent surveys suggest that amenorrhoea would be popular with many women.

Regulation and Function of LEFTY-A/EBAF in the Human Endometrium: mRNA EXPRESSION DURING THE MENSTRUAL CYCLE, CONTROL BY PROGESTERONE, AND EFFECT ON MATRIX METALLOPROTEINASES

The human endometrium is a unique tissue that is periodically shed during menstruation. Although overall triggered by ovarian steroids withdrawal, menstrual induction of matrix metalloproteinases (MMPs) and resulting tissue breakdown are focal responses, pointing to additional local modulators. LEFTY-A, a novel member of the transforming growth factor-beta family identified originally as an endometrial bleeding-associated factor (EBAF), is a candidate for this local control. We measured LEFTY-A and beta-ACTIN mRNA concentration during the menstrual cycle in vivo and found that their ratio was dramatically ( approximately 100-fold) increased at the perimenstrual phase. A similar increase was seen when proliferative explants were cultured for 24 h in the absence of ovarian steroids; this was followed by spontaneous production of proMMP-1, -3, and -9. Both responses were inhibited by progesterone. Moreover, addition of recombinant LEFTY-A to proliferative explants was sufficient to stimulate the expression of proMMP-3 and -7; this response was also blocked by ovarian steroids. Collectively, these data indicate that LEFTY-A may provide a crucial signal for endometrial breakdown and bleeding by triggering expression of several MMPs. Progesterone appears to exert a dual block, upstream by inhibiting LEFTY-A expression and downstream by suppressing its stimulatory effect on MMPs.

Vascular proliferation and vascular endothelial growth factor expression in the rhesus macaque endometrium.

The relationship between vascular endothelial growth factor (VEGF) expression and the pattern of vascular proliferation in the rhesus macaque endometrium has not been studied. In this report, we used in situ hybridization to evaluate VEGF, VEGF receptor type 1 and VEGF receptor type 2 mRNA expression during hormonally regulated menstrual cycles in ovariectomized macaques. Proliferating endothelial cells were identified by a double immunocytochemistry procedure that detected Ki-67 antigen and von Willebrand factor in the same endothelial cells. One and 2 d after progesterone withdrawal (premenstrual), VEGF mRNA was up-regulated in the glands and stroma of the superficial endometrial zones, a finding that supports our previous suggestion that VEGF may play a role in the menstrual induction cascade. During the postmenstrual repair phase, the healing surface epithelium showed a further, dramatic increase in expression of VEGF mRNA, accompanied by strong increases in signals for VEGF receptor types 1 and 2 in multiple profiles of small blood vessels immediately below the surface epithelium. This finding implicates VEGF in the early angiogenic processes associated with endometrial healing and regeneration. Vascular endothelial proliferation persisted throughout the cycle in the upper endometrial zones and showed a dramatic estrogen- dependent peak during the midproliferative phase. This proliferative peak coincided with a peak in VEGF expression in the endometrial stroma. Endothelial proliferation was also significantly correlated with the degree of stromal VEGF expression during the proliferative and secretory stages of the cycle. These results implicate VEGF of stromal origin in endometrial vascular proliferation.

Collaborative research and development on mifepristone in China to reduce unwanted pregnancies and recourse to abortion

A program proposed and executed by The Concept Foundation and funded by the Rockefeller Foundation demonstrates the feasibility of using private/public-sector collaboration for making mifepristone widely available. The application of mifepristone to emergency, luteal phase and menstrual induction contraception is being assessed in clinical research programs conducted in accordance with international standards for good clinical research. Opportunities for introduction of mifepristone in developing countries are being pursued using mifepristone produced in China in accordance with international standards of good manufacturing practice.

The Antiprogesterone Steroid, RU 486 (Mifepristone)

RU 486 (Mifepristone) represents a major development in the field of hormone antagonists as the first effective antiprogestogen. A number of therapeutic roles for the drug are envisaged. It is already being used extensively around the world for the procurement of first trimester abortion--particularly in combination with prostaglandins. It also has been shown to be effective as a cervical ripening agent and for the induction of labour. Initial human studies have involved nonviable pregnancies and more work is needed in animal models before the drug can be deemed safe for use in viable human pregnancies in the third trimester.

Progesterone receptor antagonists and prostaglandins in human fertility regulation: a clinical review

Progesterone receptor antagonists have been developed by substitutions at the 11-beta and 17 side-chain positions of the progestagen norethisterone. The most studied progesterone receptor antagonists are mifepristone (Mifegyne; Roussel-UCLAF; RU486) and ZK98734 and ZK98299 (Schering AG). These compounds bind avidly to the progesterone receptor and glucocorticoid receptor but have essentially no binding to the mineralocortocoid, oestrogen or androgen receptors. Mifepristone also binds avidly to albumin, resulting in a half-life of approximately 24 h after oral administration. Progesterone receptor antagonists can induce menstruation by a direct action upon the endometrium. They have also been shown to exert weak progesterone agonist actions in certain circumstances and to modulate pituitary hormone secretion by antagonizing the feedback actions of progesterone. Moreover, they release prostaglandin F2 alpha and E2 from human endometrium or early pregnancy decidua and reduce the metabolism of these eicosanoids. Clinically, progesterone receptor antagonists have been used in trials of menstrual regulation, abortion and induction of labour, and during treatment of breast or ovarian cancer, some forms of hypertension and meningioma. Progesterone receptor antagonists have been administered to approximately 70,000 women in 18 countries as medical abortifacients. They have been proven, especially when combined with prostaglandin analogues, to be as effective as surgical methods of termination of pregnancy. Progesterone receptor antagonists have focussed international attention on menstrual regulation, abortion and the rights of women to regulate their fertility.

The effects of progesterone receptor blockade in the luteal phase of normal fertile women

The effects of a single, variable dose (5 to 200 mg) of RU38486 (RU486) (Roussel-Uclaf, Paris, France) in the first half of the luteal phase of the menstrual cycle were studied in 30 normal fertile volunteers. Quantitative histologic techniques were employed, and the results were compared with normal ranges derived from a separate, normal, fertile population. It was found that RU486 inhibited glandular secretory activity, accelerated degenerative changes, induced various vascular changes, increased stromal but not glandular mitotic activity, and did not affect the predecidual reaction. The superiority of morphometric analysis over traditional dating criteria was demonstrated in this study of endometrial responses to an exogenously administered agent. In addition, it was found that temperature drop occurred in 56%, menstrual induction in 43%, luteolysis in 24%, mood change in 23%, and thirst sensation in 3% of women studied. Both menstrual induction and changes in hypothalamic function after the administration of RU486 occurred independently of luteolysis and so were likely to be the direct result of progesterone receptor blockade in these organs. Menstrual induction was significantly related to the dose given and the day on which RU486 was administered. Mood change was significantly related to the day on which RU486 was given. Most of the effects of RU486 occurred around 48 hours after its administration.

Why does RU486 fail to prevent implantation despite success in inducing menstruation?

The administration of RU38486 (RU486) in the luteal phase may induce menstruation, but it may not be associated with shedding of the functional layer of the endometrium. This provides an explanation why, in some cases of successful menstrual induction by RU486, pregnancy continues undisturbed. The ability of RU486 to interrupt a very early pregnancy is more likely to be related to its ability to cause shedding of the endometrium than its ability to induce menstruation.

The return to ovulation following early abortion: a comparison between vacuum aspiration and prostaglandin

The return to ovulation following early abortion (less than or equal to 56 days amenorrhea) has been assessed after both vacuum aspiration under general anesthesia (N = 14) and menstrual induction with 16,16 dimethyltrans-delta 2PGE1 methyl ester in pessary form (N = 18). The urinary excretion of hCG, total estrogen and pregnanediol was similar in each group. There was an initial rapid decline in hCG excretion (t1/2 48 h), reaching 10% of the pre-treatment value after 6 days. Twenty-nine (91%) women showed a luteal phase rise in pregnanediol excretion, with ovulation occurring on day 29 (16-37) and 24 (16-32) in the vacuum aspiration and prostaglandin groups, respectively (median (range) NS). The wide range in the return of ovarian activity was related to the variation in decline of progesterone secretion (as reflected by excretion of pregnanediol) by the corpus luteum. Asynchrony between the ovarian and menstrual cycles resulting from a delay to ovulation presents a major constraint to the use of early pregnancy interruption as a routine method of fertility control.

A controlled release form of 16,16-dimethyl-trans-Δ2-PGE1methyl ester for early abortion

The termination of early pregnancy (< 56 days amenorrhoea) has been investigated using 16,16-dimethyl-trans-Δ2-PGE1methyl ester in a controlled release preparation. The onset of crampy abdominal pain was seen after 270 ± 39 minutes and bleeding occurred after 603 ± 95 minutes. Two (15%) patients required no pain relief during treatment, however 5 (38%) requested oral analgesia, and in 6 (46%) individuals the pain was severe enough to warrant parenteral opiates. The overall success rate for complete abortion was 85%. No serious adverse effects were seen, but vomiting occurred in 2 (15%) women, and diarrhoea in 3 (23%). Although the use of this prostaglandin analogue in slow release form provides an effective treatment method for early abortion using a reduced total dose of prostaglandin, the acceptability of the drug as an agent for menstrual induction continues to be limited by the occurrence of troublesome gastro-intestinal side effects.

Pregnancy prevention by intravaginal delivery of a progesterone antagonist: RU486 tampon for menstrual induction and absorption

A progesterone antagonist (RU486) was administered to macaque monkeys by an intravaginal tampon for the achievement of both menstrual induction and absorption. The study was conducted in three parts: (1) postcoital treatment beginning 3 days after potential fertilization; (2) treatment on extended cycle days 34 to 37 after a "missed" menstrual flow after mating; and (3) luteal phase (cycle days 22 to 25) treatment in noncoital cycles. Our findings demonstrate pregnancy prevention and/or interruption when these treatments are employed.

336 Menstrual induction in the primate fertile and non-fertile cycle: Anti-progesterone RU 486 binds to endometrial progesterone receptors without affecting luteal cells

336 Menstrual induction in the primate fertile and non-fertile cycle: Anti-progesterone RU 486 binds to endometrial progesterone receptors without affecting luteal cells