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PubMed1991

Coping with extra Poisson variability in the analysis of factors influencing vaginal ring expulsions.

The vaginal ring is one method of contraception currently under investigation and development by the Human Reproduction Programme of WHO. One factor that reduces its acceptability is that some women experience involuntary expulsions of the ring. WHO have collected prospective data on 1005 women from 19 centres worldwide to investigate various aspects of ring use including factors that might affect expulsions. For each subject the data include number of expulsions, age, parity, ponderal index, number of days of ring use and health care centre. To model the factors influencing expulsion, the number of expulsions was first considered as a Poisson variate with mean directly proportional to the log of the duration of ring use. Such a model gave a poor description of the data and it appeared that the number of expulsions was considerably over-dispersed for an assumed Poisson variate. This paper examines a variety of strategies for coping with the resulting lack of fit of the model. It turns out that a truncated Poisson model gives a better description of the expulsion data and that health care centre and parity influence the rates.

Contraceptive Devices, Female↗
PubMed2006

Interleukin 1 beta is induced by interleukin 11 during decidualization of human endometrial stromal cells, but is not released in a bioactive form.

Blastocyst implantation is dependent on the differentiation of endometrial stromal cells (ESC) into decidual cells. Decidualization of human ESC in vitro is enhanced by interleukin 11 (IL11), with associated changes in gene expression. Genes downstream of IL11 may provide targets for the treatment of implantation failure or the development of non-hormonal contraceptives. This study aimed to examine the effect of IL11 on interleukin 1 beta (IL1B) mRNA and protein expression during in vitro decidualization of ESC. Cells were decidualized with 17beta-estradiol and medroxyprogesterone acetate in the presence or absence of exogenous IL11, and IL1B mRNA was quantified by real-time RT-PCR. Inactive proIL1B and bioactive IL1B in cell lysates and conditioned media were measured using specific immunoassays. Secretion of bioactive IL1B from decidualizing ESC was investigated by in vitro stimulation of decidualizing cells with lipopolysaccharide, interferon gamma or human chorionic gonadotropin. Immunohistochemistry was carried out on cycling and pregnant decidua using an antibody specific for bioactive IL1B. Exogenous IL11 increased by 28-fold the abundance of IL1B mRNA in decidualizing ESC, and total immunoreactive IL1B was also increased. However, this was not reflected in bioactive IL1B secretion from these cells, and none of the tested stimuli were able to induce its release. Bioactive IL1B was detected in vivo at very low levels and at discrete foci in late secretory phase and first trimester decidua. This regulation of latent and bioactive IL1B at the fetal-maternal interface may prime decidual cells to respond rapidly to immunological challenge or to signals from the blastocyst during implantation.

Chorionic Gonadotropin↗
PubMed2000

Risk factors for extrauterine pregnancy in women using an intrauterine device.

OBJECTIVE: To identify the risk factors for ectopic pregnancy (EP) in women using an intrauterine device (IUD). DESIGN: Case-control study. SETTING: Auvergne region (France). PATIENT(S): Women using an IUD and suffering EP (243 cases) or having an intrauterine pregnancy (140 controls). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sociodemographic characteristics, smoking, medical history, and medicines taken before the pregnancy. Type of IUD, duration of use, position and visibility of the thread at diagnosis, and presence of abnormal clinical signs. RESULT(S): Seven factors were associated with an increase in the risk of EP: histories of spontaneous abortion, IUD use, and tubal damage; progesterone IUD at the time of conception; insertion of an IUD during the month following a previous pregnancy; duration of use of the IUD in place at the time of conception; and pelvic pain resulting in medical consultation after the insertion of the IUD. Conversely, five factors were associated with a decrease in the risk of EP: history of treated low genital tract infection; history of contraception using the progestagen pill; use of paracetamol or aspirin before the pregnancy; and displacement of the IUD. CONCLUSION(S): This study suggests that the IUD itself may have an etiological role in EP.

Adult↗
PubMed1984

Complications of female sterilization: immediate and delayed.

Surgical sterilization in women has changed dramatically over the past 20 years. The development of laparoscopy and minilaparotomy have made the procedure readily available even in developing countries. In the United States, changing social values and changes in hospital regulations have done as much as technology to account for the tremendous increases in the number of women undergoing sterilization. Improved sterilization procedures have resulted in lower costs for sterilization and lowered morbidity and mortality rates. Hysterectomy for sterilization alone carries unacceptable morbidity and mortality rates. Originally, laparoscopic techniques utilized unipolar cautery. However, bowel burns, a rare but serious complication, were reported, and this led to newer techniques. These techniques, using bands, clips, and bipolar cautery, have gained increasing popularity and have eliminated many of the serious complications of female sterilization. Historically, there has been concern that tubal sterilization by any method produces, in significant numbers of patients, the subsequent gynecologic and psychologic problems called "post-tubal ligation syndrome." A review of earlier literature indicates that many of these studies have serious methodologic problems, including recall bias, inappropriate control groups, failure to elicit prior history of gynecologic or psychologic problems, and failure to account for the use of oral contraceptives or IUDs. More recent large prospective epidemiologic studies that have controlled for prior gynecologic problems and contraceptive usage have failed to show increased incidence of gynecologic sequelae in large numbers of women. However, there are some data to support the concept that in certain individuals, sterilization may result in disruption of ovarian blood or nerve supply, producing gynecologic sequelae. Additional data from these ongoing large-scale studies and others should help to elucidate this problem in the future. Pregnancy after sterilization (even excluding pregnancies present at the time of the procedure) is more common the first year after the procedure with the risk decreasing in subsequent years.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrocoagulation↗
PubMed1998

Is there any evidence for a post-tubal sterilization syndrome?

OBJECTIVE: To review the literature on menstrual and hormonal changes in women who under go tubal sterilization. DESIGN: A systematic review through MEDLINE and a literature search identified more than 200 articles in the English literature from which the most relevant were selected for this review. RESULT(S): Many authors have investigated the sequelae of female sterilization. Increased premenstrual distress, heavier and more prolonged menstrual bleeding, and increased dysmenorrhea have been reported. However, failure to control for age, parity, obesity, previous contraceptive use, interval since sterilization, or type of sterilization may have affected study results. Most studies that have controlled for these important variables have not reported significant changes, except in women who undergo sterilization between 20 and 29 years of age. CONCLUSION(S): Tubal sterilization is not associated with an increased risk of menstrual dysfunction, dysmenorrhea, or increased premenstrual distress in women who undergo the procedure after age 30 years. There may be some increased risk for younger women, although they do not appear to undergo significant hormonal changes.

Age Factors↗
PubMed1981

Normal fertility in women with post-pill amenorrhoea.

After exclusion of primary ovarian failure and causes of infertility not due to contraception 48 patients with post-pill amenorrhoea (PPA) and 47 patients whose amenorrhoea did not follow oral contraception received treatment aimed at inducing ovulation. In the patients with PPA the cumulative conception rate was 91% at 12 months from the start of treatment and 98% at 24 months. 80% gave birth to a child by 18 months and 95% by 30 months. These rates were similar to those of the non-PPA group and to previously published normal rates. Hence PPA poses no serious threat to fertility, unlike the tubal damage that may result from use of an intrauterine device. Whatever their previous menstrual history women, especially the nulliparous, who are concerned about their future fertility should be recommended oral contraception in preference to an intrauterine device.

Amenorrhea↗
PubMed2000

Factors associated with early menopause.

OBJECTIVE: An understanding of why certain factors contribute to a more rapid decline in ovarian function may, for some women, help prevent premature loss of fecundity and the subsequent impact of health problems secondary to long-term estrogen deficiency such as osteoporosis, cardiovascular disease, and possibly Alzheimer's disease. METHODS: A summary of the evidence regarding factors that have been proposed to contribute to an early onset of natural menopause is presented. These factors include cigarette smoking, race, education, parity, menstrual cycle length, the use of oral contraceptives, age at menarche, major depression, anthropometry, and handedness. RESULTS: Cigarette smoking has been found to hasten the onset of menopause by as much as one year. Lifetime number of ovulatory cycles (indicative of oocyte depletion) is also predictive of the age at natural menopause (ANP). This is consistent with the many studies that have reported early ANP among women with shorter menstrual cycles, and a later ANP among multigravid women or those who used oral contraceptives. The relationship between depressive disorder and ovarian failure is complex, involving consideration of the pharmacological effects of treatment, and is currently unclear. The findings regarding an effect of body mass index on ANP are also mixed. At this time, there is little persuasive evidence that handedness or demographic characteristics (independent of their relationship with behavioral factors like smoking) influence the ANP to any substantial degree. CONCLUSIONS: Some factors that could potentially influence ANP have been identified, but these and other avenues of investigation warrant further study.

Female↗
PubMed1999

Effects of cytochrome P450 inducers on 17alpha-ethinyloestradiol (EE2) conjugation by primary human hepatocytes.

AIMS: Our objective was to elucidate further the underlying mechanism responsible for therapeutic failures observed with concomitant administration of the oral contraceptive 17alpha-ethinyloestradiol (EE2 ) and rifampicin. METHODS: We investigated both oxidative and direct conjugative [3H]-EE2 metabolism by human liver S9 fraction and the effect of known enzyme-inducing drugs using a human hepatocyte induction model in vitro. RESULTS: Cofactor dependent [3H]-EE2 metabolism by human liver S9 fraction produced 2-hydroxy-[3H]-EE2, 2-methoxy-[3H]-EE2, and direct [3H]-EE2 sulphate and glucuronide conjugates. Only two detectable metabolites of [3H]-EE2 were produced by the S9 fraction in the presence of all cofactors: [3H]-EE2-3-sulphate (75.7+/-7.6% s. d.) and 2-methoxy-3H-EE2 (2.6%+/-0.5% s.d.). Human hepatocytes extensively metabolized [3H]-EE2 to its glucuronide and sulphate conjugates. Small amounts of a 2-methoxy-[3H]-EE2 3-conjugate, < or = 10%, was observed but no. 2-hydroxy-[3H]-EE2 was detected. An unexpected finding in our study was increased [3H]-EE2-3-sulphate production (1.5-3.3 fold, n=3 donor livers) by hepatocytes pretreated with rifampicin compared to control hepatocytes. No statistically significant increase in [3H]-EE2-3-sulphation was observed in hepatocytes pretreated with 3-methylcholanthrene, phenobarbitone, dexamethasone, or omeprazole over nontreated hepatocytes. To our knowledge, this is the first observation of sulphotransferase induction by rifampicin in human hepatocytes in vitro resulting in increased [3H]-EE2 sulphation. CONCLUSIONS: Our data indicate that the major EE2 metabolic products formed by human hepatocytes in vitro are direct EE2 conjugates with EE2 oxidation representing minor pathways. Further studies are required to establish the mechanism of sulphotransferase induction and the clinical relevance of our findings.

Adolescent↗
PubMed1996

Chlamydia trachomatis screening in family planning centers: a review of cost/benefit evaluations in different countries.

Chlamydia trachomatis is a primary cause of acute or silent salpingitis leading to infertility and ectopic pregnancy. The C. trachomatis epidemic, undiscovered in most cases, spreads, mostly in adolescents, during the years following the onset of sexual activity. As opposed to gonococcal infection which has greatly decreased, C. trachomatis cervical and urethral infection is common in young occidentals. More then 30 different studies covering 200-12,000 subjects screened in family planning centers, college women and men, students and military recruits in different parts of the USA, in Scandinavian countries and France, indicate a prevalence of 5-20% (mean 10%) in apparently healthy young females < 25 years and 5-10% in males. Female prevalence is strongly related to age, being highest (15-20%) in women < 20 years old. Several cost-benefit analyses show that the total cost of the general screening in young populations, which can easily be carried out for women in family planning centers, could save twice the cost of treatment for pelvic inflammatory disease caused by C. trachomatis and six times the total cost of C. trachomatis epidemics if late sequelae are taken into account (tubal infertility treatment, ectopic pregnancy). There is a debate among authors concerning the relative merits of total screening versus selective screening in family planning centers, the most common opinion being to do a total screening of women < 20 years old and selective screening of women 20-30 years of age with at least one risk factor, the most common risk factors being more than one partner in a year, purulent, cervical discharge, failure to use condoms and use of a contraceptive pill. Although the data clearly show that C. trachomatis screening is cost-effective, conducting of the diagnostic laboratory tests used in such screening programs should be carefully evaluated relative to cost, feasibility, specificity and sensitivity and should be adapted to the presumed prevalence in screened populations.

Adolescent↗
PubMed1996

Long-term experience of a levonorgestrel-releasing intrauterine system.

The levonorgestrel-releasing intrauterine system is a highly effective, long-acting, safe and reversible method of contraception, which offers additional health effects through its effects on menstruation. Long-term clinical studies have suggested a protective effect on pelvic inflammatory disease, have demonstrated that it is highly acceptable to the majority of women requesting effective contraception, and have shown that it may be used at any time throughout the fertile period and beyond.

Contraceptive Agents, Female↗
PubMed1989

Epilepsy and pregnancy.

Given the advantages of modern medical management, most pregnant epileptic women should experience no significant increase in seizure frequency. With good prenatal medical and obstetric care, complications of pregnancy and delivery in epileptic women differ little from those in the general population. In any case, monotherapy should be employed if possible, and anticonvulsant levels should be monitored closely during pregnancy and immediately after delivery. Dosage adjustments should be made appropriately. Since such an adjustment will usually be made in the second or third trimester, one would not expect it to produce an increased number of malformations. Trimethadione should be absolutely avoided and valproic acid used only with caution and with monitoring of alpha fetoprotein and uterine ultrasound. Although it is true that there is an increased incidence of malformations in children of epileptic women (with or without anticonvulsants), the great majority of these babies are normal. Vitamin K should be given to the mother before delivery, and the newborn should receive 1 mg vitamin K at birth. Unless the infant becomes symptomatic, breast feeding should be allowed. If seizures occur for the first time during pregnancy, the patient should be appropriately evaluated. Status epilepticus in pregnant women calls for aggressive and careful treatment. Finally, it should be remembered that oral contraceptives, especially the "mini pill," have a higher failure rate in women taking anticonvulsants. Discussing this problem with the patient is helpful.

Abnormalities, Drug-Induced↗
PubMed2003

Insertion of intrauterine devices: a comparison of experience with Mirena and Multiload Cu 375 during post-marketing monitoring in New Zealand.

AIM: To compare the incidence of reported insertion problems with the levonorgestrel-releasing intrauterine device (Mirena) with that of the copper device Multiload Cu 375. METHODS: Prescription Event Monitoring (PEM) methodology, as used in the Intensive Medicines Monitoring Programme, was used to identify cohorts of women and record events associated with insertion. RESULTS: Data were analysed from 16 159 women receiving Multiload Cu 375 between 1991 and 2001, and 3452 women receiving Mirena between 1998 and 2001. Difficult insertion was reported more often with Mirena (RR= 2.7, 95% CI = 2.2--3.3, p <0.0001). Stratified analyses suggested this was not explained by the presence of more nulliparous women in the Mirena cohort or the non-contraceptive indications for use of Mirena. Mechanical problems with the device were reported in about 1% of Mirena insertions compared with 0.01% of Multiload Cu 375 insertions and this difference was significant (p <0.001). About 2% of Mirena insertions were performed under general anaesthetic compared with 0.1% of Multiload Cu 375 insertions. Adverse reactions to insertion, including pain and vaso-vagal reaction, were more frequent with Mirena than with Multiload Cu 375 (p <0.001). CONCLUSIONS: During the period of study, insertion of Mirena was more difficult and was associated with more device problems and adverse reactions than insertion of Multiload Cu 375.

Adolescent↗
PubMed2004

Partial lipodystrophy in a girl.

A 9-year old girl presented with a 2-year history of severe loss of subcutaneous fat in her face. Her medical history included a self-limited episode of jaundice and mild fever 2 years prior. Laboratory examination revealed low serum C3 but normal serum C4. Renal function tests were normal. Low C3 can be a warning sign in patients partial lipodystrophy; it may be a harbinger of renal insufficiency. Patients with partial lipodystrophy may be predisposed to renal failure, especially after pregnancy or the use oral contraceptive pills.

Child↗