口服避孕药用量对超促排卵的影响

目的:探讨超促排卵长方案中,采用口服避孕药联合促性腺激素释放激素激动剂双降调在体外受精-胚胎移植中的应用价值。方法:共收集397例月经规律患者行体外受精-胚胎移植,均采用长方案超促排卵,降调节均为达菲林0.1 mg隔日皮下注射共7支;其中未服用妈富隆组25例(Ⅰ组),于月经第19天直接降调;常规服用妈富隆组194例(Ⅱ组),于月经第3天起服用妈富隆,1次/日,共21片,于月经第19天降调;加用剂量组(Ⅲ组)178例于月经第3天起服用妈富隆,1次/日,服用22～63片,其中服用2个周期(42片)及3个周期(63片)有9例,于月经第19～21天降调。结果:降调后E2、LH水平用药组较未用药组低,LH水平加大剂量组较常规用药组激素水平更低;而优势卵泡数未用药组较加大剂量组高;降调天数、获卵数、GN用量、HCG日内膜厚度、可用胚胎数、妊娠率、受精率、OHSS发生率无统计学差异。结论:①在体外受精-胚胎移植长方案中,对于月经规律患者应用口服避孕药可以更有效抑制激素水平,达到充分降调节,不影响内膜厚度、获卵数、妊娠率等,建议应用口服避孕药;②口服避孕药用量越大,降调后激素水平越低,优势卵泡数减少,建议应用1个周期的口服避孕药,不推荐口服避孕药长时间应用。     

One versus multiple packs for women starting oral contraceptive pills: a comparison of two distribution regimens

Background

Despite World Health Organization and International Planned Parenthood Federation recommendations to provide multiple pill cycles to new users, many programs in developing countries still give only one pill cycle to new acceptors.

Study Design

To compare provision of a single versus multiple packs of pills, new pill users in 20 matched public sector clinics in Jamaica were assigned to one of two pill regimens in which they received either one (then subsequently three) or four pill cycles at method initiation. The primary outcome was the proportion of women who used pills beyond 4 months.

Results

Among 655 women, those receiving one cycle of pills at initiation, followed by counseling and a three-pack resupply, were no more likely to be using pills after 4 months than women who received four packs at initiation (odds ratio=1.33; 95% confidence interval=0.88-2.0). In both pill regimen groups, returning late to the clinic for resupply was a problem. However, more women in the 1+3-pack regimen group returned late to study clinics to obtain their fifth cycle of pills than their counterparts in the 4-pack regimen group (53% vs. 28%).

Conclusion

Our findings support the recommendation that pill users should be given more than one cycle to start, because an extra visit for resupply contributes to clinic and provider costs. Moreover, providing more pill cycles at initiation would decrease the likelihood that women experience a gap in pill use between cycles.     

Use of oral contraceptive pills and vulvar vestibulitis: a case-control study

Vulvar vestibulitis is characterized by superficial pain during intercourse. Exploratory studies have suggested that oral contraceptives (OCs) could be associated with occurrence of vulvar vestibulitis. This 1995-1998 case-control study in Québec, Canada, sought to reassess this association. Included were 138 women with vulvar vestibulitis whose symptoms had appeared in the previous 2 years and 309 age-matched controls who were consulting their physicians for reasons other than gynecologic problems or contraception. Cases and controls were interviewed to obtain a detailed history of OC use and information on potential confounding factors. Relative risks were estimated by using logistic regression. The authors found that 4 percent of cases had never used OCs compared with 17 percent of controls. The relative risk of vulvar vestibulitis was 6.6 (95 percent confidence interval: 2.5, 17.4) for ever users compared with never users. When OCs were first used before age 16 years, the relative risk of vulvar vestibulitis reached 9.3 (95 percent confidence interval: 3.2, 27.2) and increased with duration of OC use up to 2-4 years. The relative risk was higher when the pill used was of high progestogenic, high androgenic, and low estrogenic potency. The possibility that OC use may contribute to the occurrence of vulvar vestibulitis needs to be evaluated carefully.     

Levonorgestrel-releasing intrauterine system compared to low dose combined oral contraceptive pills for idiopathic menorrhagia: a randomized clinical trial

Background

This study compared the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) to low dose combined oral contraceptive pills (COC) in the management of idiopathic menorrhagia.

Study Design

A single-center, open, randomized clinical trial. One hundred twelve women complaining of excessive menstruation who desired contraception were randomized to receive LNG-IUS or COC. Treatment failure was defined as the need for medical or surgical treatment during the follow-up. Other outcomes included: menstrual blood loss (MBL) by alkaline hematin and by pictorial blood assessment chart (PBLAC), hemoglobin levels and assessment of lost days in which physical or mental health prevented participating women from performing usual activities.

Results

At baseline, LNG-IUS (n=56) and COC (n=56) groups were comparable in age (mean±S.D.) (39.3±6.7 vs. 38.7±5.2 years, p=.637), parity (median and range) [3(1-6.4) vs.3(2-6), p=.802] and BMI (mean±S.D.) (29.6±5.9 vs. 31.1±5.7 kg/m², p=.175). Time to treatment failure was longer in LNG compared to COC group with a total of 6 (11%) patients who had treatment failure in the LNG-IUS compared to 18 (32%) in COC group with a hazard ratio of 0.30 (95% CI, 0.15-0.73, p=.007). Using alkaline hematin, the reduction in MBL (mean±S.D.) was significantly more in the LNG-IUS group (87.4±11.3%) compared to the COC group (34.9±76.9%) (p=.013). Utilizing PBLAC scores, the reduction in the LNG-IUS (86.6±17.0%) group was significantly more compared to the COC group (2.5±93.2%) (p<.001). In the LNG-IUS group, increase in the hemoglobin and ferritin levels (mean±S.D.) were noted (from 10.2±1.3 to 11.4±1.0 g/dL; p<.001; with reduction of the number of lost days (from 6.8±2.6 to 1.6±2.4 days, p=.003).

Conclusion

The LNG-IUS is a more effective therapy for idiopathic menorrhagia compared to COC.     

Vitamin nutritional status of women using oral contraceptive pills

A comparative study was conducted to assess the biochemical effects of a low-estrogen combined OC (oral contraceptive). The focus of the study was on possible biochemical effects indicative of altered nutritional status. Both low and high income women on pills were compared with others not on pills. The groups were further divided according to the duration of OC usage. Blood hemoglobin, serum Vitamin A, plasma ascorbic acid, folic acid, riboflavin, and aspartate transaminase levels were measured. Higher income women had better measures on all the indices than the low income women, indicating a better initial nutritional status. Deficiencies increased with duration of use. Results of the study show that OCs reduce the vitamin nutritional level in women. For poor women on OCs, special nutrition intervention programs should be instituted.     

Serum lipids in Chinese patients using oral contraceptive pills

Eighty-four Chinese patients attending the Family Planning Association of Hong Kong for contraception with oral contraceptive pills were randomized into 2 groups. The first group received pills containing 0.15 mg levonorgestrel and 0.03 mg ethinyl oestradiol. The second group received pills containing 0.15 mg desogestrel and 0.03 mg ethinyl oestradiol. Blood was taken after overnight fast before the use of pills for assay of serum total lipids, triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL-C). The tests were repeated at 1 month, 3 months and 6 months after the use of pills. There was a significant increase in the serum total lipids in the levonorgestrel group but not in the desogestrel group. The serum triglycerides showed a significant increase in the desogestrel group but not in the levonorgestrel group. There was no significant change in the serum total cholesterol levels in both groups. There was a significant decrease in the HDL-C in the levonorgestrel group but there was no significant change in the desogestrel group.     

Contraindications to progestin-only oral contraceptive pills among reproductive-aged women

BackgroundProgestin-only oral contraceptive pills (POPs) have fewer contraindications to use compared to combined pills. However, the overall prevalence of contraindications to POPs among reproductive-aged women has not been assessed.Study DesignWe collected information on contraindications to POPs in two studies: (1) the Self-Screening Study, a sample of 1267 reproductive-aged women in the general population in El Paso, TX, and (2) the Prospective Study of OC Users, a sample of current oral contraceptive (OC) users who obtained their pills in El Paso clinics (n=532) or over the counter (OTC) in Mexican pharmacies (n=514). In the Self-Screening Study, we also compared women's self-assessment of contraindications using a checklist to a clinician's evaluation.ResultsOnly 1.6% of women in the Self-Screening Study were identified as having at least one contraindication to POPs. The sensitivity of the checklist for identifying women with at least one contraindication was 75.0% [95% confidence interval (CI): 50.6%–90.4%], and the specificity was 99.4% (95% CI: 98.8%–99.7%). In total, 0.6% of women in the Prospective Study of OC Users reported having any contraindication to POPs. There were no significant differences between clinic and OTC users.ConclusionThe prevalence of contraindications to POPs was very low in these samples. POPs may be the best choice for the first OTC oral contraceptive in the United States.     

A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use

BackgroundUnscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP.Study DesignSubjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test.ResultsSixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03].ConclusionThe coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea.     

‘Escape’ ovulation in women due to the missing of low dose combination oral contraceptive pills

It is generally believed that in women taking anti-conceptional combined pills, the risk of pregnancy increases if a pill is missed. A study was undertaken in healthy, normally menstruating women who were given low dose combination contraceptive pills containing norethisterone acetate (NET Ac) 1 mg and ethinyl estradiol (EE₂) 30 g. In the control group, 10 women were asked to take the pills regularly daily for 21 days starting from the day 5 of the menstrual cycle. Whereas in the study group, consisting of similar women but who were sterilized, they were asked to ‘miss the pills’ on two consecutive days anywhere between day 5 to day 17 of the menstrual cycle. Thirty-five women were ‘made to miss’ the pills in the first treatment cycle and another 19 women were asked to ‘miss the pills’ in the fourth treatment cycle. Cervical mucus and lateral vaginal wall smears were studied thrice a week. Endometrial biopsy was done on day 23 ± 2. Two serum progesterone (R) levels were determined between day 22 to day 25 of the cycle.     

Effective use of hormonal contraceptives: Part I: Combined oral contraceptive pills

This systematic review examines evidence regarding when during the menstrual cycle a woman can initiate combined oral contraceptive (COC) use and what can be done if a woman misses COCs. We searched the MEDLINE and EMBASE databases for articles published from 1966 to March 2005 related to COC initiation and to the effects of late or missed COCs. We identified 11 studies related to COC initiation and 25 studies related to the effects of missed pills. Evidence from these studies suggested that taking hormonally active pills for 7 consecutive days prevents normal ovulation and that initiating COCs through Day 5 of the menstrual cycle suppresses follicular activity. Studies on the effects of missed COCs generally showed that the risk of ovulation is greatest when the pill-free interval lasts >7 days. Limitations of this body of evidence include small sample sizes that may not reflect variation in larger populations, lack of a standard measurement of ovulation and difficulty in discerning how ovulation resulting from late or missed COCs corresponds to the risk of conception.     

Adolescent compliance and side effects with Quick Start initiation of oral contraceptive pills

Adolescents' compliance with use of oral contraceptive pills has been described in the literature. The purpose of this study was to compare traditional Sunday Start to a same day (Quick Start) approach. A retrospective study of patients 22 years of age and younger was performed comparing compliance at 3 months and 12 months and side effects. The groups were divided into Quick Start (N = 77, 40%) and Sunday Start (N = 116, 60%). One hundred twenty-five (65%) patients were compliant at 3 months; 68 patients (35%) were compliant at 12 months. Quick Start users were more likely to comply at 3 months (72% vs. 56%, p = 0.059), especially if they were Caucasian (80% vs. 65%, p = 0.007), with dysmenorrhea (86% vs. 62%, p = 0.006), nulligravid (77% vs. 58%, p = 0.008), or nulliparous (73% vs. 59%, p = 0.038). There was no difference in side effects. There was no significant difference at 1 year in compliance or side effects. Findings suggest better compliance in adolescents at 3 months with the Quick Start approach while maintaining side effect profile.     

Steady-state pharmacokinetics of an extended-regimen oral contraceptive with continuous estrogen

Background

This study was conducted to evaluate the steady-state blood concentrations and potential accumulation of levonorgestrel (LNG) and ethinyl estradiol (EE) administered for up to 84 days and EE alone for 7 additional days as an extended-regimen 91-day oral contraceptive (OC).

Study design

An open-label, single-site study was conducted in 30 healthy female volunteers. Subjects received daily doses of 0.15 mg LNG/0.03 mg EE for 84 consecutive days followed by 0.03 mg EE alone for 7 days. Pharmacokinetic (PK) monitoring was conducted on Days 1, 21, 84 and 91.

Results

The observed plasma concentrations of LNG after 84 days and of EE after 84 and 91 days were comparable to the steady-state concentrations observed at 21 days. Pharmacokinetic parameters over the 24-h dosing period were similar at all time points measured after achieving steady-state plasma concentrations.

Conclusion

This study demonstrated that an extended-regimen OC providing 84 days of LNG/EE and 7 days of EE alone has a PK profile similar to a 28-day conventional OC regimen and does not result in any additional accumulation of these hormones.     

Postponement of withdrawal bleeding with a monophasic oral contraceptive containing desogestrel and ethinylestradiol.

This study investigated the ability of a monophasic sub-50 oral contraceptive, containing desogestrel and ethinylestradiol, to postpone withdrawal bleeding in normal healthy women. In the analyzed group of 105 regular users of Marvelon, about 75% did not experience any vaginal bleeding during the 21 days of postponement. A 95% confidence interval was calculated which suggests that the percentage of women able to postpone their withdrawal bleeding successfully for 19 days ranges between 67.0% and 83.5%. Women with no vaginal blood loss in the postponement period were more willing to try this method of postponement again, compared to women who experienced vaginal blood loss in the postponement period. This difference was statistically significant. Nevertheless, the majority of women with vaginal blood loss were also willing to try this method again if necessary. The study results suggest that Marvelon offers an effective and acceptable method of postponing withdrawal bleeding for three weeks for most regular users of this contraceptive.     

The evaluation of guingestanol acetate as a low dose oral contraceptive

Four hundred patients completed 4,370 cycles of treatment using quingestanol acetate, 300 mcg daily. Twelve pregnancies occurred resulting in a failure rate of 3.3 per 100 woman years. Seven of these pregnancies were considered drug failures giving a rate of 1.9 per 100 woman years. Cycle length, amount and duration of flow were not significantly different from pretreatment. Intermenstrual bleeding occurred in 51% of the patients and in 12% of cycles; amenorrhea occurred in 20% of the patients and in 5% of cycles. Endometrial biopsies showed normal patterns in 92% of specimens taken during the follioular phase of the menstrual cycle and in 67% of those taken during the luteal phase. An anovulatory pattern was shown in 14% taken during the luteal phase. Numerous laboratory tests demonstrated no abnormalities which could be associated with therapy. The discontinuance rate of 15% for drug-related reasons during the three years of this program indicated favorable patient acceptance. This study indicated that quingestanol acetate used at a daily dose of 300 mcg is a safe and effective oral contraceptive.     

Outcomes of extended oral contraceptive regimens with a shortened hormone-free interval to manage breakthrough bleeding

OBJECTIVE: To evaluate in a clinical practice setting the acceptance, continuation and variability of extending the active interval of oral contraceptives (OCs) with introduction of a shortened hormone-free interval (HFI) to manage breakthrough bleeding. METHODS: A retrospective review was undertaken of patients seen by one obstetrician/gynecologist and counseled on extending the active interval of OCs with a shortened HFI of 3-4 days to manage bleeding. Electronic medical records were searched for the phrase "extending the number of active pills" for patients counseled between January 1, 2000, and January 31, 2003, with follow-up through January 31, 2004. A structured query of each patient's initial and follow-up records was performed. RESULTS: The 220 patients counseled on the extended regimen were 14-52 years of age (mean 36.4, SD 9.3 years). At initial counseling before extending, the majority of patients cited more than one reason for using OCs in the standard fashion with 59% using OCs for noncontraceptive reasons. Reasons for extending the active interval of OCs included premenstrual symptoms (45%), dysmenorrhea/pelvic pain (40%), heavy withdrawal bleeding (36%), menstrual associated headaches (35%), convenience (13%), acne associated with menses (10%) and other (15%). Of the 181 patients with follow-up data, 174 (96%) attempted an extended regimen with 121 (67%) continuing to do so at last follow-up. Follow-up intervals ranged from 0.3 to 3.8 years (mean 1.6 years). Using Kaplan-Meier product limit survival analysis, 60% of patients continued using extended patterns of OCs for more than 2 years. For 121 currently extending, the HFI varied from 0 to 7 days with 88% utilizing a 0 to 4 day HFI. CONCLUSIONS: Sixty percent of patients offered extending the active interval and shortening the HFI of OCs initiate and continue this pattern for more than 2 years without serious sequelae or pregnancy while individually directing both the number of days of continuous pills and the length of the HFI.