Management of disorders of ovulation

This review article evaluates the management of disorders of ovulation by first examining the specific conditions covering hypothalamic disorders, polycystic ovary syndrome and hyperprolactinaemia. Treatment options for disorders of ovulation depend on the clinical presentation, the underlying cause and the woman's wishes. Those who seek fertility require treatment to induce ovulation, and this treatment should be offered in conjunction with assessment of other factors relevant to fertility, including semen analysis and the exclusion of pelvic pathology. The uses of clomiphene citrate, gonadotrophins, gonadotrophin releasing hormone (GnRH), metformin, laparoscopic surgery and in vitro fertilization (IVF) are discussed. Ovulation should not be induced in women who do not wish to conceive. These women usually seek a diagnosis and cycle control. This is best achieved using cyclical progestogens or an oestrogen-progestogen pill, and treatment choice depends on the woman's oestrogen status and her contraceptive needs. The final section concentrates on adverse outcomes of induction ovulation including multiple pregnancy, ovarian hyperstimulation syndrome (OHSS) and ovarian carcinoma.     

The influence of Microgynon and Diane-35, two sub-fifty ovulation inhibitors, on voice function in women

The early days of oral contraceptives showed some evidence that these medications may have caused undesirable side effects on the voice, mainly in terms of virilization. In a random study carried out at the university hospitals of Jena and Berlin (Charité), two more recent drugs were tested in this regard, one containing cyproterone acetate (Diane-35^®) and the other one levonorgestrel (Microgynon^®), both from Schering. Ninety-one patients took part in extensive clinical and instrumental phoniatric investigations of voice function over a period of one year. No significant side effects on the voice could be proven for the two preparations. Gynecological and clinical effects of both Diane-35^® and Microgynon^® were similar during the one-year study period. Women taking Diane-35^® had less intracyclic bleedings and amenorrhea. Also, acne was more favorably influenced by Diane-35^®.     

Suppression of the endogenous luteinizing hormone surge by the gonadotrophin-releasing hormone antagonist Cetrorelix during ovarian stimulation

Surges of luteinizing hormone (LH) that result In luteinizationbut occur prematurely with respect to the diameter of the leadingfolilde, prevent attempts to induce multiple follicular maturationfor in-vitro fertilization (IVF) in a significant number ofwomen. We examined the possibility of blocking premature LIIsurges by the administration of Cetrorelix, a potent antagonistof gonadotrophin-releasing hormone (GnRH), in a study Including20 patients, some of whom had previously shown premature LHsurges. All patients were treated with human menopausal gonadotrophins(HMG) starting on day 2. From day 7 until the induction of ovulationby human chorionic gonadotrophin (HCG) the GnRII antagon Cetrorelixwas given daily. HCG was injected when the dominant fofficlehad reached a diameter of >18 mm and oestradlol concentrationwas >300 pg/ml for each follicle having a diameter of >15mm. Oocyte collection was performed 36 h later by transvaginalultrasound puncture, followed by IVF and embryo transfer. Thehormone profiles of these patients and the results of IVF andembryo transfer are comparable to those treated with GnRH agonistsand HMG. However, less time and especially less HMG Is neededin comparison to patients stimulated with a long agonist protocol.Hence, treatment with Cetrorelix proved to be much more comfortablefor the patient. In this study we showed that combined treatmentwith gonadotrophins and the GnRH antagonist Cetrorelix is apromising method for ovarian stimulation in patients who frequentlyexhibit premature LH surges and therefore fall to complete treatment.     

Anisotropic crystalline microstructures in dendritic arborizations of dried mid-cycle cervical mucus: surface morphology and crystallographic study.

Studies using scanning electron microscopic techniques permitted characterization of the nature and structure of the anisotropic elements present in dried preparations of mid-cycle cervical mucus. Sodium and potassium sulphates were located in the dehydrated matrix either isolated or bound to the dendrites. Depending on crystallization conditions, they appeared as well-formed individual crystals or as spherulites.     

Bradykinin potentiates LH-induced follicular rupture in the rat ovary perfused in vitro

The possible role of bradykinin as a modulator of LH-induced ovulation was investigated using a model of the in-vitro perfused rat ovary. Ovaries from immature rats, primed with pregnant mare's serum gonadotrophin (PMSG; 20 IU), were perfused in vitro for 20 h, starting on the morning of induced proestrus. Stimulation in vitro with luteinizing hormone (LH; 0.1 microgram/ml) resulted in 3.4 +/- 1.2 ovulations per treated ovary, whereas no ovulations occurred in the unstimulated group. Bradykinin (5 microM) added to the perfusion system at 0, 2.5, 5, 7.5 and 10 h gave two ovulations in one ovulating ovary out of five ovaries perfused. When LH was combined with bradykinin, added to concentrations of 1 microM and 5 microM at the above-mentioned five time points, the numbers of ovulations were 12.2 +/- 2.7 and 15.6 +/- 3.7 per treated ovary, respectively. Bradykinin (5 microM), administered as a single dose concomitantly with LH, resulted in no further increase in the ovulation rate (3.6 +/- 1.6). Bradykinin did not affect cyclic AMP or steroid release from unstimulated or LH-stimulated ovaries. These data indicate a role of bradykinin in the ovulatory process of the rat, potentiating LH-induced ovulations.     

促黄体激素释放激素与小剂量人绝经期促性腺激素诱导排卵

３例下丘脑闭经（ＨＡ）妇女及２例多囊卵巢综合征（ＰＣＯＳ）妇女采用脉冲式静脉注射促黄体激素释放激素（ＬＨ—ＲＨ）诱导排卵，在ＬＨ—ＲＨ治疗后１０天左右加用小剂量人绝经期促性腺激素。３例ＨＡ病人的３个治疗周期均排卵，其中１例妊娠并足月分娩一男孩。另一周期未加ｈＭＧ亦排卵。２例ＰＣＯＳ病人经４个周期治疗均失败。无卵巢过度刺激综合征发生。ＬＨ—ＲＨ与小剂量ｈＭＧ联合疗法对恢复下丘脑闭经妇女的生殖功能是一种安全、有效的方法。     

Regulation of corpus luteum function

The effects have been studied of different ovulation inductionregimens [either domiphene citrate or buserelin in combinationwith human menopausal gonadotrophin (HMG)] on the circulatingconcentrations of progesterone, oestradiol, relaxin and humanchorionic gonadotrophin (HCG) during the first trimester ofpregnancy. Ovulation induction with clomiphene resulted in elevatedconcentrations of gonadotrophins in both phases of the cycle,while during ovulation induction with buserelin, gonadotrophinconcentrations were elevated in the follicular phase only. Theconcentrations of all corpus luteum products were greater inclomiphene pregnancies compared with spontaneous pregnancies,but only oestradiol and relaxin concentrations were greaterin clomiphene pregnancies compared with buserelin pregnancies.The concentrations of HCG were significantly reduced in clomiphenepregnancies compared to natural pregnancies. Relaxin concentrationswere significantly higher from 7 weeks gestation in buserelincompared with spontaneous pregnancies, while progesterone, oestradioland HCG concentrations were not consistently different. Consistentassociations were found between relaxin and HCG concentrationsin spontaneous pregnancies and between the concentrations ofrelaxin and both progesterone and oestradiol in pregnanciesachieved after ovulation induction. These data suggest that(i) given the similarity in the circulating concentrations ofHCG, the relatively lower circulating gonadotrophin concentrationsduring the luteal phase of the cycle of conception result inreduced circulating concentrations of oestradiol and relaxin;while in the case of relaxin this effect is partially reversible,there is no evidence that this is so for oestradiol; (ii) synthesisof progesterone in the corpus luteum is less affected by lowerconcentrations of gonadotrophins during the luteal phase; (iii)ovulation induction with clomiphene results in pregnancies withlower concentrations of HCG, suggesting that trophoblast functionmay be impaired; and (iv) corpus luteum function is linked withplacental steroidogenesis.     

Relation of supplementary feeding to resumptions of menstruation and ovulation in lactating postpartum women

Background Resumption of menstrual cycles is one of the indicators for restoration of reproductive capability in postpartum women. However, menstruation does not necessarily mean that ovulation has taken place. The aim of this study was to investigate the relation of supplementary feeding to return of menstruation and ovulation after delivery. Methods A questionnaire was used to obtain data from 101 breastfeeding mothers. The following elements were analyzed: age, education level, breastfeeding practice, time of return of menstruation, contraceptive practice, and starting time of supplementary feeding during the lactation at intervals of 6 weeks to 18 months after delivery. The ovulation was continuously monitored by ultrasonography and basal body temperature (BBT) measurement.Results By ultrasonography, 53 of the 101 women (52.5%) had the first ovulation (follicle >1.8 cm in diameter) within 154 days after delivery on average, among whom 11 (10.9%, 11/101) had restoration of ovulation within 4 months and 42 (41.6%, 42/101) had it after 4 months. In women with follicles >1.8 cm in diameter (n=53), the menstruation resumed (138±84) days after delivery, and the supplementary feeding was started at (4.0±1.1) months, which were significantly earlier than those in the women with follicular diameter <1.7 cm (n=48; (293±88) days, (5.1±1.3) months; t=9.003, P<0.01 and t=4.566, P<0.01). In the women with follicles >1.8 cm in diameter, 30 had return of menstruation before the end of ultrasonographic monitoring, while only 8 in the women with follicular diameter <1.7 cm had menstrual resumption at the same time (χ²=16.91, P<0.01). The starting time of supplementary feeding was positively correlated with the time of the restoration of menstruation (n=100, r=0.4764, P<0.01) and first ovulation after delivery (n=53, r=0.5554, P<0.01). In this series, no woman had pregnancy within 18 months postpartum.Conclusion Supplementary feeding can affect the restoration of menstrual cycles and ovulation in lactating postpartum women.     

The position of diagnostic laparoscopy in current fertility practice

In everyday clinical practice, it is not always clear if and when exactly in the fertility work-up a diagnostic laparoscopy should be offered. The aim of this review is to analyse the available evidence with respect to alternative diagnostic methods for detecting tuboperitoneal infertility and with respect to the position of diagnostic laparoscopy in women with infertility. A literature search of the National Library of Medicine and the National Institutes of Health (PubMed) was performed using the key words 'diagnostic laparoscopy and infertility'. The study methodology was carefully considered in an effort to present conclusions preferably based on randomized controlled trials (RCTs). The routine use of diagnostic laparoscopy for the evaluation of all cases of female infertility is currently under debate. According to data published in retrospective non-controlled studies, diagnostic laparoscopy after several failed cycles of ovulation induction enables the detection of a significant proportion of pelvic pathology amenable to treatment. A Cochrane review has shown that laparoscopic ovarian diathermy in clomiphene-resistant polycystic ovarian syndrome is at least as effective as gonadotrophin treatment, and results in a lower multiple pregnancy rate. The role of laparoscopy before the start of treatment with intrauterine insemination is controversial, according to one RCT. In women with bilateral ultrasonically visible hydrosalpinges, two RCTs have demonstrated increased implantation and pregnancy rates in IVF cycles after salpingectomy. Although RCTs which have studied the benefit of laparoscopic surgery in moderate or severe endometriosis are still lacking, its value has generally been accepted. In conclusion, some specific clinical settings, solid evidence is available to recommend the use of diagnostic laparoscopy in current fertility practice. There is however a need for more RCTs to answer remaining questions regarding its value in the diagnosis and treatment of some patients with infertility.     

中医周期疗法在PCOS不孕症患者促排卵周期中的疗效观察

目的:观察中医周期疗法结合西药促排卵治疗对多囊卵巢综合征(PCOS)不孕症患者排卵率、妊娠率及肌注人绒毛膜促性腺激素日(HCG日)子宫内膜厚度、类型,未破裂卵泡黄素化综合征(LUFS),克罗米芬(CC)反应不良及卵巢过度刺激综合征(OHSS)发生率的影响。方法:选取PCOS不孕症患者58例,随机分为对照组(克罗米芬+补佳乐),治疗组(克罗米芬+补佳乐+中医周期疗法),各29例,治疗3个月经周期,比较两组排卵率、妊娠率及HCG日子宫内膜厚度、类型,LUFS,CC反应不良及OHSS发生率。结果:对照组、治疗组总周期排卵率分别为64.38%,80.28%,两组比较差异具有统计学意义(P0.05)。治疗组HCG日A型子宫内膜所占比例高于对照组,两组比较差异具有统计学意义(P0.05)。治疗组妊娠率高于对照组,但两组比较差异无统计学意义。两组LUFS,CC反应不良及OHSS发生率均低于对照组,两组比较差异无统计学意义。结论:中医周期疗法结合西药促排卵治疗,可提高PCOS患者的排卵率,改善子宫内膜容受性,增加妊娠率,并减少LUFS,CC不反应的发生率。