Follicular administration of a cyclooxygenase inhibitor can prevent oocyte release without alteration of normal luteal function in rhesus monkeys

BACKGROUND: Prostaglandins (PG), produced by the follicle just before ovulation, appear to act locally to promote follicle rupture and oocyte release. METHODS: To determine whether administration of PG synthesis inhibitor directly into the primate follicle would prevent ovulatory events, serum estradiol was used to predict the day of the ovulatory LH surge in rhesus monkeys. On the day before or the day of the LH surge, vehicle (n = 9), the PG synthesis inhibitor indomethacin (10(-6) or 10(-5) mol/l final concentration; n = 8), or 10(-5) mol/l indomethacin + 1 micro g/ml PGE(2) (n = 3) was injected into the follicular fluid of the pre-ovulatory follicle. In some animals, luteal phase estrogen and progesterone were measured in daily serum samples. Other animals were ovariectomized 3 days after follicle injection; ovaries were examined for verification of follicle rupture and oocyte release. RESULTS: Follicle injection of indomethacin [10(-6) mol/l (n = 4) or 10(-5) (n = 4) mol/l final concentration] or vehicle (n = 6) did not alter luteal function. Examination of serial sections of removed ovaries confirmed follicle rupture and the absence of oocytes in vehicle-injected follicles (n = 3). Trapped oocytes were observed in 4/8 indomethacin-injected follicles, though several ovaries with trapped oocytes had experienced follicle rupture. Oocytes were not detected in the ruptured, luteinizing follicles from indomethacin + PGE(2)-injected monkeys (n = 3). CONCLUSIONS: Follicular administration of indomethacin can prevent oocyte release without inhibition of follicle rupture or disruption of subsequent luteal function. The ability of PGE(2) to prevent indomethacin-induced ovulatory failure suggests a critical role for locally produced PGE(2) in the process of oocyte release in primates.     

Ovulation and risk of epithelial ovarian cancer

Incessant ovulation is thought to be one of the primary causes of epithelial ovarian cancer. However, the effects of ovulation at different ages and of the various exposures or events that suppress ovulation have not been established. We used data from an Australian case-control study of 791 ovarian cancer cases and 853 controls to examine the effect of ovulation on ovarian cancer risk. The total number of lifetime ovulations was calculated using information provided in a monthly contraceptive/reproductive calendar, as well as incorporating other information such as average menstrual cycle length. An increase of 1 year's worth of ovulation was associated with a 6% increase in risk of ovarian cancer (95% confidence interval [CI] = 4-8%). Ovulations in the 20-29-year age group were associated with the greatest risk, with a 20% increase in risk associated with each year of ovulation during this age period (95% CI = 13-26%). When the effects of different exposures that suppress ovulation were compared, there was an indication that some factors may have a greater effect than others. These findings support the theory that incessant ovulation is a major contributor to the occurrence of ovarian cancer and suggest that ovulations during the 20s may be those most associated with disease risk.     

小鼠体外成熟与激素超排卵母细胞核型分析

目的：评价激素超排(HIO)和体外培养成熟(CVM)两种方法对小鼠卵母细胞染色体的影响。方法：通过HIO与CVM分别获得100个、80个成熟小鼠卵母细胞,制备染色体标本进行核型分析。结果：在HIO组,超单倍体率、非整倍体率、染色体结构畸变率、结构畸变卵母细胞率、退化卵母细胞率和染色体分离均数依次为2,0％、4．0％、2．0％、2．0％、8．0％和0．13;在CVM组,上述实验参数依次为4．O％、8．O％、7．5％、6．3％、12．5％和O．325;两组所有实验参数经统计学处理没有显著差异。结论：经体外培养成熟的与经激素超排的小鼠卵母细胞其质量和染色体核型没有本质上的差异。将此结果外推到人类,提示未成熟卵母细胞经体外培养成熟在人类辅助生殖领域具有广泛的应用前景。     

Influence of the angiotensinogen gene on the ovulatory capacity of mice

Objective: The tissue-bound ovarian renin-angiotensin system (OVRAS) is critically involved in ovulation in humans and rodents. Mice with disruption and overexpression of the angiotensinogen gene (Agt) have been previously generated. We investigated the influence of varying Agt gene expression on the ovulatory capacity and early embryonic development in mice.

Design: Observational study of genetically altered mice and their response to a superovulation protocol.

Setting: Academic research institution.

Animal(s): Mice with varying copy numbers of Agt (one copy: N = 48; two copies: N = 51; three copies: N = 20; four copies: N = 24).

Intervention(s): Superovulation protocol, oocyte culture.

Main Outcome Measure(s): Number of oocytes harvested, early embryonic development of zygotes, evaluation of ovarian histology, serum estradiol measurements.

Result(s): The mean number of oocytes harvested was greatest in wild-type mice (two copies of Agt, 39.9 ± 14) with a reduction of ovulatory capacity in mice overexpressing Agt (three copies [34.8 ± 11.7] and four copies [31.2 ± 12.4], P = .026). Mice with one copy of Agt showed a slight decrease of ovulatory capacity compared to wild-type mice (35.8 ± 15.2, P = .29). Ovarian histology, serum estradiol levels, and early embryonic development were independent of the Agt genotype.

Conclusion(s): Overexpression of Agt was associated with reduced ovulatory capacity, but with none of the other parameters that were evaluated. These findings support an important role of the ovarian renin-angiotensin system in the process of follicular rupture.     

Pharmacokinetics of 10 mg of mifepristone

The results of several randomized studies have verified the efficacy of 10 mg mifepristone in emergency contraception. In the present study we characterized the pharmacokinetics of 10 mg mifepristone. Eight healthy female volunteers received a single oral dose of mifepristone on the day 10 or 11 of their menstrual cycle. Blood samples were collected at 0, 1, 2, 4 and 8 h, daily for the next 6 days and on day 10 after mifepristone. Mifepristone concentrations were determined by radioimmunoassay preceded by column chromatography. A peak level of 1.41 ± 0.31 μmol/L (mean ± SD) was measured at 1 h. Individual elimination phase half-lives varied from 15.3 to 26.8 h, the mean (± SD) value being 19.6 ± 4.50 h. Serum mifepristone concentrations exceeded 10 nmol/L in all volunteers for an average of 4.9 days. The pharmacokinetic data on 10 mg mifepristone are in line with previous pharmacokinetic and clinical data, and encourage further development of the 10-mg dose in emergency contraception.     

Severe OHSS: yes, there is a strategy to prevent it!

Effective measures to prevent ovarian hyperstimulation syndrome (OHSS) remain controversial. It became almost 'common knowledge' that there is no strategy that may completely prevent OHSS. Extensive clinical experience (albeit not derived from prospective randomized studies) clearly documents the ability of a single administration of gonadotrophin-releasing hormone (GnRH) agonist to effectively trigger ovulation, while completely eliminating any threat of clinically significant OHSS. This strategy cannot be used if the pituitary is down-regulated (as is the case in most assisted reproductive cycles today), however, the newly-introduced GnRH antagonists open new opportunities for implementing this strategy, since the pituitary preserves its responsiveness to GnRH agonists. Combining GnRH antagonist-based ovarian stimulation (particularly in 'high responders'), with GnRH agonist-driven ovulation triggering will make severe OHSS a disease of the past in assisted reproduction.     

Expanding access to emergency contraception.

Emergency contraception (EC) is safe and has the potential to prevent unwanted pregnancies. However, use remains low in most settings, due to a range of barriers to access. This paper reviews key issues related to EC and describes recommendations reached during the Women's Health Alliance pre-Congress workshop, held in advance of the FIGO 2006 World Congress. The working group concluded that national societies of obstetrics and gynecology can play an important role in increasing access to this unique contraceptive method.     

葆癸胶囊联合西药对多囊卵巢综合征患者抗苗勒管激素影响的临床观察

目的观察葆癸胶囊联合西药治疗多囊卵巢综合征的临床疗效及其对抗苗勒管激素(AMH)的影响。方法将68例多囊卵巢综合征患者随机分为治疗组和对照组,每组34例。对照组予炔雌醇环丙孕酮片治疗,治疗组在对照组治疗措施基础上加服葆葵胶囊治疗。两组疗程均为3个月经周期,药后随访3个月,观察月经失调疗效,比较抗苗勒管激素(AMH)水平及血清中雌二醇(E2)、促卵泡生成素(FSH)、黄体生成激素(LH)、总睾酮(T)的变化情况。结果 (1)治疗组、对照组临床总有效率分别为85.3%、58.8%;组间月经失调疗效比较,治疗组明显优于对照组(P0.05)。(2)治疗前及停药3个月后组内比较,两组AMH水平差异均有统计学意义(P0.05);组间停药3个月后比较,AMH水平差异有统计学意义,治疗组明显低于对照组(P0.05)。(3)治疗前及停药3个月后组内比较,两组LH、LH/FSH、T水平差异均有统计学意义(P0.05),而E2、FSH水平差异无统计学意义(P0.05);组间停药3个月后比较,T水平差异有统计学意义(P0.05)。结论葆癸胶囊联合西药治疗多囊卵巢综合征,与单纯服用西药相比,能更加有效地改善患者的月经失调,降低其血清T及AMH水平。     

Ovarian stimulation in women undergoing in-vitro fertilization and embryo transfer using recombinant human follicle stimulating hormone (Gonal-F) in non-down-regulated cycles

In order to assess the efficacy and safety of recombinant humanfollicle stimulating hormone (FSH) in routine clinical use,ovarian stimulation with recombinant human FSH was performedin 71 patients prior to in-vitro fertilization (IVF) withoutgonadotrophin-releasing hormone (GnRH) analogues in a multicentre,non-comparative study. Human chorionic gonadotrophin (HCG) wasadministered to 58 patients (81.7%), 15 of whom underwent 19cycles with an initial dosage of three ampoules daily of recombinantFSH and 43 of whom underwent 152 cycles with four ampoules dailyfrom day 3 onwards. No significant differences were detectedbetween these two groups in all test parameters. The mean durationof treatment was 9.06 and 8.86 days respectively with a meannumber of 24.06 and 23.25 vials of recombinant human FSH administered.A mean number of 6.26 and 5.88 oocytes respectively was collected.The number of transferred embryos was 2.4 and 2.2. A clinicalpregnancy rate of 23.8% (10 out of 42) per transfer was achieved(30.9 and 20.6% respectively). Local tolerance of s.c. administrationwas excellent. Mild pain at the injection site was the dominantfinding in <20% of patients. Two cases of ovarian hyperstimulationsyndrome were noted. Recombinant human FSH is very attractiveto patients because it can be self-administered s.c. and thepreparation does not come from a human source. In conclusion,these data support the safety and efficacy of recombinant humanFSH in routine use for IVF.