输卵管切除术对体外受精-胚胎移植中控制性超促排卵的影响

目的：探讨输卵管切除术对体外受精-胚胎移植（IVF-ET）周期超促排卵中卵巢反应性的影响.方法：选择因异位妊娠行一侧输卵管切除、双侧输卵管切除的患者以及双侧输卵管未切除的管性不孕患者,观察在IVF-ET中卵巢对控制性超排卵的反应.结果：3组患者年龄、促性腺激素用量、获卵数、受精数以及妊娠率差异无统计学意义.单侧输卵管切除的患者中输卵管切除侧卵巢获卵数少于对侧,但差异无统计学意义.结论：输卵管切除术对IVF-ET周期中卵巢反应性以及妊娠率无明显影响.输卵管积水患者拟行IVF-ET前预防性切除输卵管是可行的.     

Evaluation and Treatment of Low Responders in Assisted Reproductive Technology: A Challenge to Meet

Purpose: To investigate the various methods of evaluationand treatment of patients with a low response to controlledovarian hyperstimulation in assisted reproductive technologies (ART). Methods: Review and analysis of relevant studies publishedin the last decade, identified through the literature and Medlinesearches. Results: While a universally accepted definition for lowresponders is still lacking, these patients are reported torepresent about 10% of the ART population. Several ovarianreserve screening techniques have been proposed; however,currently the best-characterized and most sensitive screeningtools available are the basal day 3 serum follicle-stimulatinghormone level and the clomiphene citrate challenge test.When abnormal, these tests allow physicians to counselpatients that their prognosis for conception is poor. Althoughthe presence of a normal result does indicate better long-termchances for conception, an age-related decline in fecundityremains and patient age should still be considered whencounseling patients with normal screening results. Severalstimulation protocols have been applied in the low-responsegroup with varying success. Recent studies show that theuse of a minidose gonadotropin-releasing hormone-agonistprotocol may result in significantly decreased cycle cancellationsas well as increased clinical and ongoing pregnancies,and thus is proposed as a first-line therapy. Studies evaluatingsupplementary forms of treatment to the ovulation inductionregimen show improved outcome when pretreating withoral contraceptives, whereas there seems to be no benefitfrom cotreatment with growth hormone or glucocorticoids.Blastocyst culture and transfer and assisted hatching in lowresponders are still under evaluation, whereas natural cyclein vitro fertilization may be used in cases of repeated failuresas a last option before resorting to oocyte donation or adoption.Future possible forms of treatment like in vitro maturationof immature human oocytes, cytoplasm, and nucleartransfer currently are experimental in nature and their efficacyhas still to be proven.Conclusions: The evaluation and treatment of low respondersin ART remains a challenge. Understanding of the underlyingetiology and pathophysiology of this disorder may helpthe clinician to approach it successfully.     

Mechanism of participation of medial preotic area in the hippocampal inhibition of ovulation

Bilateral hippocampal (HPC) stimulation with anodal direct current on the afternoon of proestrus blocked sponstaneous ovulation in 87.5% of the Wistar rats subjected to the experiments. The incidence of the ovulation block by this procedure was reduced to 16.7% on bilateral injection of 0.25 μg picrotoxin into the medial preoptic area (mPOA) preceding as well as following the stimulation. Ovulation was also blocked in 53.8% of the animals by bilateral injection of 50.0 μg GABA into mPOA, while only 20.0% animals showed a blockade of ovulation of HPC stimulation can be simulated mPOA. These observations indicate that blockade of ovulation by saline injection into by local injection of GABA into mPOA while the effect of stimulation can be blocked by local injection of picrotoxin. Thus, indicating the possibility of GABA being neurotransmitter involved at the level of mPOA for mediating the inhibitory hippocampal influence on ovulation.     

The role of hypothalamic serotonin (5HT) before ovulation in immature rats treated with pregnant mare serum (PMS).

(1) PCPA methyl ester (10 mg/rat i.p.) inhibits induced ovulation in immature rats treated with pregnant mare serum (PMS). It also suppresses the preovulatory surges of LH and FSH, but not those of oestradiol or progesterone. (2) There is an increase in hypothalamic 5HT levels in the aftermoon and hypothalamic 5HIAA levels in the evening of the two days studied (days 28 and 29 of life). This occurs whether or not PMS was given on day 27. (3) The antiovulatory effects of PCPA are only seen when it is given on the afternoon or evening of the day before the pre-ovulatory gonadotrophin surge, i.e. on day 28 over the period of raised hypothalamic 5HT metabolism. (4) PCPA reduces 5HT metabolism in the hypothalamus within 2 hr of administration and its anti-ovulatory effect can be overcome by 5-hydroxytryptophan. This indicates that hypothalamic 5HT activity is essential for the gonadotrophin surge. (5) The anti-ovulatory effect of PCPA can be overcome by progesterone, LH and FSH but not oestradiol.     

Relationship between follicle size at insemination and pregnancy success

Administration of gonadotropin-releasing hormone (GnRH) induces a surge of luteinizing hormone and ovulation in a variety of species, including human beings. Our objectives were to determine the effect of follicle size at the time of ovulation on corpus luteum function and establishment and maintenance of pregnancy in cows in which ovulation was either spontaneous or induced with GnRH. GnRH-induced ovulation of follicles < or approximately = 11 mm in diameter resulted in decreased pregnancy rates and increased late embryonic mortality. This decrease in fertility was associated with lower circulating concentrations of estradiol on the day of insemination, a decreased rate of increase in progesterone after insemination, and, ultimately, decreased circulating concentrations of progesterone. In contrast, ovulatory follicle size had no apparent effect on fertility when ovulation occurred spontaneously. Follicles undergoing spontaneous ovulation do so at a wide range of sizes when they are physiologically mature. Therefore, administration of GnRH to induce ovulation likely initiates a preovulatory gonadotropin surge before some dominant follicles attain physiological maturity. GnRH-induced ovulation of follicles that are physiologically immature has a negative impact on pregnancy rates and late embryonic/fetal survival. These observations in cattle may have implications for assisted reproductive procedures in human beings.     

A phase I study of the pharmacokinetics, pharmacodynamics, and safety of single- and multiple-dose anastrozole in healthy, premenopausal female volunteers

OBJECTIVE: To evaluate the pharmacokinetic, pharmacodynamic, and safety profiles of the aromatase inhibitor anastrozole in healthy, premenopausal women. DESIGN: Phase I, single-center study. SETTING: Infertility clinic. PATIENT(S): Twenty-six women with regular ovulatory cycles: 20 received either a single dose of 5 mg, 10 mg, 15 mg, or 20 mg anastrozole, or remained untreated; 6 received five daily doses of 10 mg or 15 mg anastrozole. INTERVENTION(S): Anastrozole was administered on cycle day 2 for the single-dose groups and on days 2-6 for the multiple-dose groups. Ultrasound follicular development and endometrial biopsies were performed. Safety was determined from adverse event reports and laboratory parameters. MAIN OUTCOME MEASURE(S): Pharmacokinetics, pharmacodynamics, and safety. RESULT(S): The pharmacokinetics of anastrozole were linear, predictable, and consistent with previously published data in healthy volunteers. In the single-dose groups, E2 levels reached their nadir 3-6 hours after administration, decreasing by an average of 39% from baseline. Follicle-stimulating hormone levels rose by 13%, 52%, 49%, and 75% in the 5-mg, 10-mg, 15-mg, and 20-mg groups, respectively, at approximately 24 hours after dosing. Most subjects recruited just one mature follicle, with no apparent effect on endometrial maturation. No safety concerns were noted. CONCLUSION(S): Anastrozole was well tolerated and suppressed E2 levels, with a resultant increase in FSH.     

A randomized trial of letrozole versus clomiphene citrate in women undergoing superovulation

OBJECTIVE: To compare the effects of the aromatase inhibitor letrozole (7.5 mg) and clomiphene citrate (CC; 100 mg) in women undergoing superovulation and IUI. DESIGN: Prospective randomized trial. SETTING: University teaching hospital. PATIENT(S): We studied a total of 238 cycles of superovulation and IUI in women with idiopathic infertility. INTERVENTIONS: Patients were randomized into treatment with 7.5 mg of letrozole daily (74 patients, 115 cycles) or 100 mg of CC daily (80 patients, 123 cycles). MAIN OUTCOME MEASURE(S): Number of follicles, endometrial thickness, pregnancy rate, and miscarriage rate. RESULT(S): The mean age, parity, and duration of infertility in both groups of patients were similar. There was no significant difference between the total number of developing follicles in the letrozole (5.7 +/- 3.7) and in the CC groups (4.8 +/- 2.5). The number of follicles of > or =14 mm and of >18 mm were 2.1 +/- 1.2 and 1.4 +/- 0.7 in the letrozole group, and 1.7 +/- 0.9 and 1.1 +/- 0.5 in the CC group, respectively. No difference was found in the endometrial thickness between the two groups (7.1 +/- 0.2 mm in the letrozole group, 8.2 +/- 5.9 mm in the CC group). The pregnancy rate per cycle was 11.5% in the letrozole group and 8.9% in the CC group. Four of the 11 pregnancies in the CC group resulted in a miscarriage (36.6%). CONCLUSION(S): Superovulation and IUI with letrozole and CC are associated with similar pregnancy rates, but the miscarriage rate is higher with CC. The ideal dose of letrozole remains unknown and further study is needed.     

Histological analysis of the ‘critical point’ in follicular development in mice

Aim:  To histologically examine ovarian follicular development in cycling mice.
Methods:   Mice were observed at 13:00 h at each stage of the estrous cycle. The ovaries were cut into complete serial sections. All sections were observed, and the size of each follicle was measured by using a micrometer. Follicles with advanced atresia were excluded and non-atretic healthy follicles were differentiated from atretic follicles.
Results:  The measurement of the number of follicles in each stage of the estrous cycle, with reference to their size, showed that in each mouse, the number of small healthy follicles (100–249 µm in average diameter) was approximately 100 for all stages and the number of medium-sized healthy follicles (250–349 µm) was close to 20 in only the metestrus and diestrus stages. In contrast, large healthy follicles (≥350 µm) showed marked changes throughout the estrous stage. Many healthy large follicles were observed in the proestrus stage, but they disappeared in the estrus stage, which suggests that they have ovulated. This was supported by observations of oocytes resuming meiosis in large healthy follicles.
Conclusion:  As follicular atresia was frequently observed in follicles of 250–399 µm diameter, this size range may be a 'critical point' for atresia. The results suggest that there is a 'critical point' in follicular development, and that only follicles that pass this point will ovulate, while those that do not will become atretic follicles. (Reprod Medical Biol 2004; 3 : 141–145)     

Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene citrate-resistant polycystic ovary syndrome. Impact on women's health-related quality of life

BACKGROUND: Ovulation induction with gonadotrophins is the standard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Laparoscopic electrocautery of the ovaries is an alternative treatment modality, leading to a comparable cumulative pregnancy rate. In deciding which treatment to opt for, women's health-related quality of life (HRQoL) should be taken into account. METHODS: A total of 168 CC-resistant women with PCOS were randomly assigned to receive either the electrocautery strategy, entailing laparoscopic electrocautery of the ovaries followed by CC and recombinant FSH (rFSH) if anovulation persisted, or ovulation induction with rFSH. We assessed women's HRQoL with the standard questionnaires Short Form-36, Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression Scale, administered before randomization and 2, 12 and 24 weeks thereafter. RESULTS: The intention to treat analysis revealed no significant differences between the treatment groups on any of the scales at any point during follow-up. In women without an ongoing pregnancy, those treated with rFSH showed significantly more depressive symptoms than women allocated to the electrocautery strategy, with or without CC, although differences were small. CONCLUSIONS: Overall, HRQoL was not affected in both groups. In women still under treatment, rFSH was slightly more burdensome for women's HRQoL than electrocautery with or without CC.     

Is there a future for ovulation induction in the current era of assisted reproduction?

The clinical use of medical induction of ovulation in normogonadotrophic anovulatory women (WHO II), including polycystic ovary syndrome, is increasingly questioned. However, we believe that this treatment modality still represents a highly effective means of fertility treatment in women with low pregnancy chances without intervention. A conventional treatment algorithm involving clomiphene citrate (CC) followed by FSH induction of ovulation may result in a 71% cumulative singleton live birth rate. In attempts to improve treatment outcome further and reduce complication rates, new compounds such as insulin-sensitizing agents or aromatase inhibitors are currently used increasingly. Approaches such as patient selection for different treatment modalities on the basis of initial screening characteristics and alternative protocols for FSH ovulation induction may also be proposed to render treatment algorithms more patient tailored and therefore improve overall outcomes. More research is needed in this area, rather than referring these patients to assisted reproduction prematurely. This may lead to a more individually tailored approach for ovulation induction in a given patient, resulting in a further improvement of the balance between chances for success versus complications.