Human chorionic gonadotrophin priming for fertility treatment with in vitro maturation.

BACKGROUND: In vitro maturation (IVM) is a fertility treatment that involves the transvaginal retrieval of immature oocytes, and their subsequent maturation and fertilisation. Although the live birth rate is lower than conventional in vitro fertilisation (IVF) with ovarian stimulation, it is a useful treatment, as it avoids the risk of ovarian hyperstimulation syndrome (OHSS). Women with polycystic ovaries (PCO) or polycystic ovarian syndrome (PCOS) are at an increased risk of OHSS. Thus, IVM may be a more useful treatment in this patient group.Strategies to maximise the maturation rates of the immature oocytes are important. This review focuses on the administration of human chorionic gonadotrophin (hCG) prior to immature oocyte retrieval. OBJECTIVES: To determine the effectiveness and safety of hCG priming in subfertile women who are undergoing IVM treatment in the context of assisted reproduction. SEARCH METHODS: We searched the following electronic databases up to 29 August 2016: Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL. We also searched the trial registries ClinicalTrials.gov and WHO ICTPR to identify ongoing and registered trials. We sought recently published papers not yet indexed in the major databases, and reviewed the reference lists of reviews and retrieved studies as sources of potentially relevant studies. There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared hCG priming with placebo or no priming in women undergoing IVM. We also included RCTs that compared different doses of hCG, or the timing of oocyte retrieval. The primary outcomes were live birth rate and miscarriage rate per woman randomised. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, and with a third author, assessed risk of bias and extracted data. We contacted the original authors where data were missing. For dichotomous outcomes, we used the Mantel-Haenszel method to calculate odds ratios (OR). For continuous outcomes, we calculated the mean differences (MD) between treatment groups. We assessed statistical heterogeneity using the I² statistic. We assessed the overall quality of the evidence using GRADE methods. MAIN RESULTS: We included four studies, with a total of 522 women, in the review. One of these studies did not report outcomes per woman randomised, and so was not included in formal analysis. Three studies investigated 10,000 units hCG priming compared to no priming. One study investigated 20,000 units hCG compared to 10,000 units hCG priming. Three studies only included women with PCOS (N = 122), while this was an exclusion criteria in the fourth study (N = 400).We rated all four studies as having an unclear risk of bias in more than one of the seven domains assessed. The quality of the evidence was low, the main limitations being lack of blinding and imprecision.When 10,000 units hCG priming was compared to no priming, we found no evidence of a difference in the live birth rates per woman randomised (OR 0.65, 95% confidence intervals (CI) 0.24 to 1.74; one RCT; N = 82; low quality evidence); miscarriage rate (OR 0.60, 95% CI 0.21 to 1.72; two RCTs; N = 282; I² statistic = 21%; low quality evidence), or clinical pregnancy rate (OR 0.52, 95% CI 0.26 to 1.03; two RCTs, N = 282, I² statistic = 0%, low quality evidence). Though inconclusive, our findings suggested that hCG may be associated with a reduction in clinical pregnancy rates; 22% of women who received no priming achieved pregnancy, while between 7% and 23% of women who received hCG priming did so.The study comparing 20,000 units hCG with 10,000 units hCG did not report sufficient data to enable us to calculate odds ratios.No studies reported on adverse events (other than miscarriage) or drug reactions. AUTHORS' CONCLUSIONS: This review found no conclusive evidence that hCG priming had an effect on live birth, pregnancy, or miscarriage rates in IVM. There was low quality evidence that suggested that hCG priming may reduce clinical pregnancy rates, however, these findings were limited by the small number of data included. As no data were available on adverse events (other than miscarriage) or on drug reactions, we could not adequately assess the safety of hCG priming. We need further evidence from well-designed RCTs before we can come to definitive conclusions about the role of hCG priming, and the optimal dose and timing.

Everolimus, an mTOR pathway inhibitor, is highly successful on ovarian hyperstimulation syndrome by reducing ovarian weight and progesterone levels: a preclinical experimental randomized controlled study.

The usefulness of various pathways inhibitors, Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), Infliximab, a monoclonal antibody which blocks the tumor necrosis factor-a (TNF-a), Erlotinib, a tyrosine protein kinase inhibitor of the epidermal growth factor receptor (EGFR), Metformin, an activator of AMP-activated protein kinase enzyme (AMPK) and vascular permeability reducers were explored in an ovarian hyperstimulation syndrome (OHSS) rat model. Sixty-three female Wistar rats were randomly divided in seven groups. The control group received saline, while the OHSS group received recombinant -- follicle-stimulating hormone (rec-FSH) for four consecutive days. The other five groups received rec-FSH for 4 d and Everolimus daily, Infliximab once, Erlotinib daily, Metformin daily and Vitamin C daily, respectively. All groups received human chorionic gonadotropin (hCG) at the fifth day. The efficacy of Everolimus administration for various intervals was also explored. Significantly reduced ovarian weight was observed in the Everolimus group (rec-FSH + hCG + mTOR inhibitor) compared to the OHSS group (p < 0.001). The Everolimus group also showed the lowest progesterone (PRG) concentration (p = 0.007). The Erlotinib group (rec-FSH + hCG + EGFR inhibitor) presented with the lowest graafian follicle number, while the Everolimus group was characterized by the lowest corpus luteum number. The vascular permeability and the estradiol levels did not differ between groups. Finally, the Everolimus intra-comparison showed no difference in all measured outcomes. Studying the different pathways linked to vascular endothelial growth factor (VEGF) pathway, we conclude that targeting mTOR pathways is beneficial for reducing ovarian weight and PRG levels in an OHSS animal model.

Quality of sexual life of women on oral contraceptive continued-regimen: pilot study.

INTRODUCTION: To date, women may use flexible oral contraceptive (OC) regimens. AIM: The aim of this study was to evaluate the quality of sexual life of healthy women on continued-regimen OCs. METHODS: Fifty women (age range 18-38) were enrolled. The Female Sexual Function Index (FSFI) and the Short Form-36 (SF-36) questionnaires were used to investigate, respectively, sexual behavior and the quality of life (QoL) of women on OC for 72 days with a 4-day hormone-free interval, for two cycles. Both the FSFI and the SF-36 were administered before starting OC intake, at the first (72-82 days) and the second (144-154 days) follow-ups. MAIN OUTCOME MEASURE: The main outcomes are the FSFI and the SF-36 questionnaires. RESULTS: The FSFI score obtained at the first follow-up detected a worsening with respect to baseline score (P < 0.05). The score obtained at the second follow-up detected an improvement with respect to both the baseline and the first follow-up total scores (P < 0.05). QoL improved at the first follow-up only as regards body pain (P < 0.05), and at the second follow-up as regards: physical role, body pain, general health, vitality, and social function (P < 0.05). CONCLUSIONS: The use of continued-regimen OCs is able to improve the sexual behavior and the QoL of women.

[Venous thromboembolism in adolescents associated with fourth-generation oral contraceptives]. / Venöse Thromboembolien bei Jugendlichen mit Kontrazeptiva der vierten Generation.

Venous thromboembolism (VTE) is a rare, but feared adverse drug reaction of combined oral contraceptives. Modern oral contraceptives contain novel progestins, which are suspected of causing thrombotic events more frequently than well-known progestins. Drospirenone is one of those new fourth-generation progestins with antiandrogenic and antimineralocorticoid effects. Especially girls and young women do not only wish for contraception, but also for positive effects on skin and body weight. In the last decade, however, the safety of this progestin was often under discussion.A detailed literature search was conducted to obtain an overview of currently available data on the risk of VTE among girls and young women using drospirenone-containing contraceptives. It appears that drospirenone-containing contraceptives have a similar increase in risk as third-generation oral contraceptives and antiandrogens. Compared to second-generation contraceptives containing the progestin levonorgestrel there is an approximate 2-fold risk increase (1.0 to 2.8-fold) in women aged 10-55 years. Accurate data regarding the risk in the age group under 18 years are lacking. Nevertheless, the risk of VTE appears to be higher in young -women during the first months of treatment. Until more data for nov-el progestins are available and the safety profile is well defined well-studied second-generation oral contraceptives with low dose estrogen and better risk-benefit ratio should be preferred in young women. In any case, all patients should be comprehensively informed regarding the benefits and risks of each contraceptive method.

A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization.

STUDY QUESTION: Is it possible to define an optimal dose of hCG in combination with rFSH from the first day of stimulation in the GnRH agonist protocol applied to IVF? SUMMARY ANSWER: Supplementation with hCG from the first day of stimulation may increase the number of top-quality embryos per patient. Daily doses of hCG up to 150 IU are compatible with good live birth rates. A ceiling level of estradiol (E(2)) was reached with hCG doses above 100 IU/day. A positive dose-response was seen for pre-ovulatory progesterone, but concentrations remained below values for which an impairment of endometrial receptivity has been previously reported. We suggest a large clinical trial to be proceeded with a group given 100 IU hCG daily versus a control group. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Prospective multicentre studies have indicated increased live birth rates and increased number of top-quality embryos when low doses of hCG were associated with FSH. We analysed the clinical, embryological and endocrine aspects of adding increasing doses of hCG to rFSH from the first day of stimulation for IVF. DESIGN: A prospective randomized, controlled, open-label dose-response pilot study was conducted between February 2009 and June 2010 at Copenhagen University Hospital, Rigshospitalet, Denmark. Adequate allocation concealment was assured from sequentially numbered, opaque, sealed envelopes prepared from a computer-generated list. Scoring of the embryos was done in an assessor-blinded way. PARTICIPANTS AND SETTING: Endocrinologically normal IVF patients aged 25-37 years, BMI 18-30 kg/m(2), regular cycles and FSH <12 IU/l, were treated with a fixed dose of rFSH 150 IU/day and randomized to daily hCG dose of 0, 50, 100 or 150 IU from Day 1 of stimulation. Primary end-point was the total number of top-quality embryos on Day 3. DATA ANALYSIS METHOD: Data were analysed by analysis of variance, Kruskal-Wallis test, chi-squared test or Poisson distribution count. MAIN FINDINGS: A total of 62 patients were randomized into four hCG dose groups: Dose 0 (D0; n= 16), Dose 50 (D50; n= 15), Dose 100 (D100; n= 16) and Dose 150 (D150; n= 15). Two patients in D150 were withdrawn after randomization because of major (10- to 30-fold) hCG dosing errors, leaving 13 patients in this group. Thus, the results are based on the per protocol population. The mean numbers of top-quality embryos per patient were D0: 0.8 ± 1.2, D50: 0.5 ± 0.7, D100: 1.2 ± 1.7 and D150: 1.5 ± 1.7 (P= 0.04). All pregnancies were singleton gestations, and the live birth rates per started cycle were D0: 25%, D50: 27%, D100: 25% and D150: 31% (P= 0.98). Steady state level of serum (s)-hCG was reached on Day 6 of stimulation. S-hCG levels (IU/l) on the day of hCG administration were D0: <0.1, D50: 3.1 (2.6-3.6), D100: 5.5 (4.1-7.4) and D150: 11.0 (8.9-13.6) (P< 0.01). The patients receiving hCG supplementation were stratified by 33 and 66% percentiles into three groups according to the concentration of s-hCG on Day 6 of stimulation: 0.5-3.5 IU/l (n= 16), 3.5-8.0 IU/l (n= 14) and 8.0-21.1 IU/l (n= 14). The mean numbers of top-quality embryos in the three groups were 0.5 ± 0.9, 1.1 ± 1.8 and 1.5 ± 1.5, respectively (P= 0.03). The progesterone increments from stimulation Day 1 to the day of hCG triggering were D0 = 49%, D50 = 79%, D100 = 110% and D150 = 160% (P= 0.02). S-androstenedione level was highest in D150 (P< 0.01). S-E(2) was 2-fold higher in the D100 and D 150 compared with D0 (P= 0.09). BIAS, LIMITATION, GENERALISABILITY: Our study has a limited sample size. Supplementation with daily hCG dose up to 150 IU throughout stimulation has never been used before. Hence, this had to be tested in a small study before conducting a larger trial. STUDY FUNDING/COMPETING INTERESTS: Ferring Pharmaceuticals, Research and Development, provided funds for the endocrine measurements. CLINICALTRIAL.GOV REGISTRATION: NCT00844311.

More harm than good: the lack of evidence for administering misoprostol prior to IUD insertion.

The administration of misoprostol prior to insertion of an intrauterine device has become a widespread practice. Because of its utility for cervical ripening before procedures such as dilatation and curettage, misoprostol has been assumed to be a safe and useful adjunct both to facilitate the ease of insertion of an IUD and to reduce the pain experienced by women during this procedure. As this practice has become more widely used, a body of literature has evolved to assess whether or not it truly improves the IUD insertion experience for providers and patients. A literature search showed that six controlled trials have been carried out to assess this practice (one is reported in abstract form only). The dosing and route of administration vary between the trials; however, there are quite consistent findings that not only does misoprostol administration not improve the ease of insertion of IUDs but it also leads to increased unpleasant side effects. The routine use of misoprostol for IUD insertion should be abandoned.

Can oral contraceptives cause vestibulodynia?

AIM: To describe the clinical course of a young woman who developed vestibulodynia with introital dyspareunia while on oral contraceptive (OCs) and to provide a possible explanation for the etiology of her symptoms as well as her recovery after treatment. METHODS: A single case is presented including subjective reporting, laboratory evaluation, and quantitative sensory testing. RESULTS: After topical hormonal therapy, the patient reported resolution of her dyspareunia and and her laboratory values normalized.

Comparison of the efficacy and safety of phloroglucinol and magnesium sulfate in the treatment of threatened abortion: A meta-analysis of randomized controlled trials.

BACKGROUND: To compare the clinical efficacy and safety of phloroglucinol (PHL) and magnesium sulfate (MS) in the treatment of threatened abortion through systematic review. METHODS: Foreign databases, such as the Cochrane Library, PubMed and EMBASE, and Chinese databases, including the China Biology Medicine disc (SinoMed), China National Knowledge Infrastructure (CNKI), Chongqing VIP (VIP) and WanFang Data, were searched. Published randomized controlled trials (RCTs) documents obtained from these databases were included if they were associated with the research objective. The search timeframe was from the beginning of the establishment of each database to May 2018. Document selection, data abstraction and document quality evaluation were independently performed by 2 investigators. A combined analysis of the data was performed for those documents that fulfilled the study requirements; Rev Man 5.3 and Stata 12.0 software were used to compare and analyze the 2 drugs in terms of the total effective rate (TER), rate of adverse events, time required to relieve uterine contractions, onset time, time of complete relief of uterine contraction symptoms, medication duration and length of hospital stay. RESULTS: A total of 21 RCT trials were included in the present research, according to the inclusion criteria. However, the quality of the included studies was low. The meta-analysis suggested that the TER and drug onset time of PHL were higher than those for MS, while the rate of adverse events, the time required to relieve uterine contractions, time to complete relief of uterine contraction symptoms, drug continuous treatment time and length of hospital stay were shorter than those for MS. CONCLUSION: The clinical efficacy of PHL is better than that of MS, and PHL obviously results in fewer adverse reactions than MS. However, due to poor quality of evidence, high quality, multi-center RCTs with large samples are required for further verification.

Central precocious puberty in a boy with 22q13 deletion syndrome and NOTCH-1 gene duplication.

The 22q13 deletion syndrome or Phelan-McDermid syndrome is a neurodevelopmental disorder associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic faces. We report the occurrence of central precocious puberty in a boy diagnosed with Phelan-McDermid syndrome. At the age of 1 year, our patient presented with increased testicular volume for his age, bone age advancement and growth acceleration. Stimulated gonadotropin levels demonstrated a premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. Central precocious puberty was treated with gonadotropin-releasing hormone (GnRH) analog. Molecular diagnosis with array-comparative genomic hybridization (CGH) revealed a major deletion of 5.8 Mb at the 22q13 chromosomal region and a 25 kb duplication at the 9q34.3 region that included the NOTCH-1 gene. On the background of 22q13 deletion syndrome and data from animals on the effect of abnormal NOTCH-1 gene expression on kisspeptin neuron formation, we discuss the probable role of Notch signaling in the premature activation of the HPG axis.

Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty.

BACKGROUND: Triptorelin is an established treatment for central precocious puberty (CPP) as 1- and 3-month formulations. The current triptorelin 22.5 mg 6-month formulation is approved for prostate cancer therapy. This is the first study in patients with CPP. METHODS: The efficacy and safety of the triptorelin 6-month formulation in CPP were investigated. The primary objective was to evaluate the efficacy in achieving luteinizing hormone (LH) suppression to pre-pubertal levels at month 6. This was an international, non-comparative phase III study over 48 weeks. Eighteen medical centers in the US, Chile and Mexico participated. Forty-four treatment naïve patients (39 girls and five boys) aged at treatment start 2-8 years for girls and 2-9 years for boys with an advancement of bone age over chronological age ≥1 year were to be included. Triptorelin was administered im twice at an interval of 24 weeks. LH, follicle stimulating hormone (FSH) (basal and stimulated), estradiol (girls), testosterone (boys), auxological parameters, clinical signs of puberty and safety were assessed. RESULTS: Forty-one patients (93.2%) showed pre-pubertal LH levels (stimulated LH ≤5 IU/L) at month 6 and maintained LH suppression through month 12. The percentage of patients with LH suppression exceeded 93% at each time point and reached 97.7% at month 12. No unexpected drug-related adverse events were reported. CONCLUSIONS: The triptorelin 6-month formulation was safe and effective in suppressing the pituitary-gonadal axis in children with CPP. The extended injection interval may improve compliance and increase comfort in the management of CPP.

Monitoring treatment of central precocious puberty using basal luteinizing hormone levels and practical considerations for dosing with a 3-month leuprolide acetate formulation.

BACKGROUND: Peak gonadotropin-releasing hormone or agonist (GnRHa) stimulated luteinizing hormone (LH) testing with leuprolide acetate (LA) is commonly used to document suppression during therapy for central precocious puberty (CPP). The objective of the study was to investigate suitability of using basal LH levels to monitor GnRHa treatment and to determine optimal transition from 1-month to 3-month LA formulations via a post hoc analysis of a randomized, open-label, 6-month study. METHODS: A total of 42 children with CPP, pretreated with 7.5-, 11.25-, or 15-mg 1-month LA formulations were randomized to 11.25- or 30-mg 3-month LA. Basal LH/peak-stimulated LH levels were measured at weeks 0, 4, 8 and 12. Positive/negative predictive values and sensitivities/specificities were determined for basal LH vs. LH-stimulation results. RESULTS: Pretreatment with any 1-month formulation for the most part did not affect continuation of suppression after transitioning to 3-month formulation (mean peak-stimulated LH levels remained < 4 IU/L). Basal LH predicted suppression escape (basal LH-level cutoff ≥ 0.6 IU/L predicted 70% of those failing suppression). Tolerability was similar, regardless of dose. CONCLUSIONS: Our data indicate that a basal level of <0.60 IU/L is adequate for monitoring suppression approximately two-thirds of the time. Furthermore, the effectiveness and safety of 3-month LA treatments are not influenced by previous CPP therapies.

Quinacrine sterilization (QS): the ethical issues.

QS has generated debates that are ultimately grounded in various principles, norms, and values. Through a careful analysis of opposing arguments, this paper focuses on two ethical principles claimed by both sides, namely: respect for life and beneficence. Though issues surrounding QS are complex, from the common ground of these two principles, this paper proposes a course of action that addresses many of the concerns from both points of view.

Quinacrine sterilization (QS) experience in the Philippines: a preliminary report.

OBJECTIVE: The first clinical trial of Quinacrine Sterilization (QS) in the Philippines was undertaken in Cebu City on January 10, 2000, to evaluate the acceptability, safety, effectiveness and side effects of this technology. We intend to recruit 500 patients to utilize this technique for limiting family size. For the purposes of this report, our cut-off date is April 11, 2003. METHODS: Over more than two years, QS was performed on 36 volunteer patients. After careful explanation of the procedure and given the opportunity to ask questions, they had signed an informed consent. The trial involved transcervical insertion of 252 mg quinacrine in the form of pellets, and placed at the tip of the uterine fundus on two occasions, a month apart. Condoms were routinely provided to all patients except those on oral contraceptive pills and DMPA after the first insertion to be used for six weeks after the second one. As the numbers are small, no statistical evaluation was called for. RESULTS: The accumulated experience was 515 woman-months. There were no pregnancies, neither ectopic nor intrauterine: Adverse events (AE) were mild. Some patients complained of a yellow discharge and itching. Fifty percent experienced mild abdominal discomfort which was easily managed with mefenamic acid. CONCLUSIONS: Although this is a small study, we believe that QS is both safe and effective and we are strongly encouraged to continue to offer this nonsurgical sterilization method to our patients.

The rate of ectopic pregnancy for 24,589 quinacrine sterilization (QS) users compared to users of other methods and no method in 4 provinces in Vietnam, 1994-1996.

OBJECTIVE: To determine the rates of ectopic pregnancy with the use of quinacrine sterilization (QS) compared to other methods and no method (non-users). METHODS: Four provinces were selected for their above average numbers of women who had undergone QS: Nam Dinh, Nam Ha, Hai Duong and Hung Yen. Case histories related to surgical treatment of all ectopic pregnancies in these 4 provinces from 1994 through 1996 were collected from all hospitals by researchers from the Ministry of Health in June 1997. Using a questionnaire designed for this study, 120 physicians interviewed every woman in her home who had had an ectopic pregnancy during this period. If deceased, a family member was consulted. All interviews were completed in September 1998. The numbers of users of each method and nonusers were calculated from service statistics and demographic data. RESULTS: Based on 2,551,355 woman-years of exposure, the rate of ectopic pregnancy among users per 1000 woman-years was calculated to be: 0.26 with QS; 0.42 with surgical sterilization (TL) and IUD; 0.45 with the Pill; 0.50 with condoms; 0.78 relying on withdrawal; and 1.18 among non-users. CONCLUSION: Ectopic pregnancy rates for QS, TL, IUD and the Pill were similar and much lower than the rate for non-users of contraception.

Quinacrine sterilization (QS) among high-risk women: a study of 134 cases.

OBJECTIVE: To determine if quinacrine sterilization (QS) is safe and effective in women at high risk for surgery. METHODS: A trial was initiated at the Government Medical College in Patiala, India, in December 1993. Patient intake was terminated in July 1999 and the cut-off date for this analysis was March 31, 2003. Using a modified IUD inserter, seven 252 mg quinacrine pellets with 50 mg of diclofenac were transcervically inserted into the uterus. DMPA 150 mg was administered IM at the time of the first insertion as a back-up contraceptive. This same combination was inserted a month later. A total of 134 women underwent QS. Of these, 92 were considered to be at high risk for surgery, 27 were afraid of surgery or voluntarily opted for QS, and 15 had had failed surgical sterilization or surgery was found not to be technically feasible. Follow-up was scheduled for 1, 3, 6 and 12 months, and then annually after the second insertion or whenever side effects or complications were experienced. RESULTS: Mean follow-up was 7.2 years. No pregnancies or serious complications were experienced. CONCLUSION: QS is a safe and effective option for women at high risk of surgical complications.

The acceptability, efficacy and safety of quinacrine non-surgical sterilization (QS), tubectomy and vasectomy in 5 provinces in the Red River Delta, Vietnam: a follow-up of 15,190 cases.

OBJECTIVES: To compare the safety, efficacy and acceptability of quinacrine sterilization (QS), tubectomy and vasectomy in Vietnam. METHODS: This study was initiated in January 1998 and completed in February 2000. A sample of 9 districts in 5 provinces, where the prevalence of QS was known to be high, was selected. Every person sterilized in these 9 districts between January 1, 1988 and March 31, 1998 was identified and systematically interviewed by family planning clinicians who had received special training for this project. RESULTS: A total of 15,982 sterilization users were identified and 15,190 were interviewed and examined, including a gynecologic exam, if needed: a follow-up rate of 95%. Of those interviewed, 9,753 used tubectomy, 3,734 used QS and 1,703 used vasectomy. All three methods were found to be safe, although morbidity associated with tubectomy was more serious than with QS or vasectomy. No deaths were reported. After more than 5 years of follow-up, tubectomy had the lowest failure rate: 1.0%, followed by 4.1% with vasectomy. A pregnancy rate of 13.2% was reported with quinacrine, although only a small fraction of these failures were confirmed. A strong preference for QS was found. CONCLUSION: QS has an important role to play in sterilization services in Vietnam.

8-year follow-up in a randomized trial of one vs two transcervical insertions of quinacrine pellets for sterilization in Indonesia.

OBJECTIVE: To evaluate the efficacy of one vs two insertions of quinacrine and the long-term safety of quinacrine sterilization (QS) 8 years after the procedure in Indonesia. METHODS: Between March 1993 and September 1995, a randomized trial was conducted in 6 academic centers in Indonesia. In February 2003, a follow-up study was undertaken in Bandung, one of those centers. This survey required a home visit of each woman. A questionnaire was designed to elicit information regarding current general health status, method failure, pregnancy outcomes and other contraceptive methods now used by women who experienced failures. Among the 70 patients receiving a single insertion of quinacrine pellets, 14.3% had become pregnant. There were no pregnancies among the 30 who received 2 insertions. All the women were found to be in good health. No long-term side effects or complications were identified. CONCLUSION: The two-insertion protocol is unmistakably superior to the single insertion. This study provides further evidence that QS is a safe contraceptive method.

Quinacrine sterilization (QS) in Syria: a preliminary report on 297 cases.

OBJECTIVES: To evaluate the safety, efficacy and acceptability of quinacrine sterilization (QS) in Syria. METHODS: From July 2001 to December 2002, 297 women who requested permanent sterilization volunteered for QS either in my private practice or my local family planning center in Aleppo, Syria. The standard protocol was used: 252 mg of quinacrine in the form of 7 pellets are deposited at the uterine fundus with a modified CuT IUD inserter during the proliferative phase of the menstrual cycle. This procedure is repeated 4 weeks later. DMPA was injected at the time of the first insertion for temporary contraception. Every sterilized woman has had a monthly checkup visit until the cut-off date for this report, including a beta HCG pregnancy test. All procedures were performed by the author. The cut-off date for this report was June 11, 2003. RESULTS: The single pregnancy was ectopic. Four women (1.3%) complained of severe pain. Moderate pain was experienced by 13.1% while the remaining women felt mild pain, all easily treated. The remaining side effects were minor and also easily treated. Oligomenorrhea and amenorrhea affected 29% of the women and lasted for several months. Immediate side effects are similar to reports from other researchers. CONCLUSIONS: Results thus far regarding efficacy are encouraging. QS has proven to be acceptable.

10-year follow-up of women who elected quinacrine sterilization (QS) in Wonosobo, Central Java, Indonesia.

OBJECTIVES: To evaluate the safety and efficacy of quinacrine sterilization (QS) in Indonesia. METHODS: During the period, August 1992 to October 1993, 200 women who had requested surgical sterilization volunteered for QS at the Wonosobo Regency Hospital, Central Java Province, Indonesia. The protocol called for transcervical insertion of 252 mg of quinacrine in the form of 7 cylindrical pellets and 55.5 mg of ibuprofen with a CuT-IUD (Kimia Farma) inserter during the proliferative phase of the menstrual cycle. A second procedure was done 4 weeks later. The technique used is essentially the same as inserting a CuT-IUD. Follow-up was scheduled at 6, 12, 24 and 48 months after the last insertion. In March 2003 additional monitoring was completed. RESULTS: The 10-year cumulative pregnancy rate was 4.3 per 100 women with a follow-up rate of 93%. No pregnancies had occurred among these women since the 4-year follow-up. No long-term side effects or complications were reported. CONCLUSIONS: After 10 years of use, QS was found to be safe and reasonably effective.