Involvement of leukocytes and cytokines in the ovulatory process and corpus luteum function

The role of leukocytes and cytokines in ovarian physiology isnow established, although the function of each cell type andcytokine remains to be determined in detail. Current knowledgeof these effects on follicle development, ovulation, luteinizationand luteotrophic process and luteolysis is reviewed. It is possiblethat further research will help to unravel some of the clinicalmysteries in ovarian function, including polycystic ovary syndrome,premature menopause, ovulatory disorders, and luteal phase defect.Furthermore, the increasing use of cytokines and their antagonistsin clinical practice may have significant effects upon reproductivefunction.     

Induction of follicular growth and production of a normal hormonal milieu in spite of using a constant low dose of luteinizing hormone in women with hypogonadotrophic hypogonadism

This study was designed to examine ovarian performance, i.e.follicular growth, normal steroidogenesis and luteal phase function,following the administration of multiple increasing doses ofhuman follicle stimulating hormone (FSH) with a constant lowdose of luteinizing hormone (LH) in women with isolated hypogonadotrophichypogonadism. Human meno–pausal gonadotrophin (HMG) wasused in the first treatment cycle, starting with 150 IU of LHand 150 IU of FSH per day, for 7 days. The dose was increaseddaily with 75 IU of LH and 75 IU of FSH for another 7 days ifno response was detected by serial ultrasound measurements andserumoestradiol determinations. In the second treatment cycle,a constant dose of 75 IU of LH (using HMG) was administeredper day and up to 150 IU of FSH (using urofollitrophin) wassupplemented. If no response was detected after 7 days of treatment,the dose of FSH was increased. For the final stage of ovulationinduction, human chorionic gonadotrophin (HCG) was administeredin the presence of at least one follicle >17 mm in diameterbut with no more than three follicles >16mm in diameter.To verify the adequacy of the luteal phase, a pharmacokinetic/pharmacodynamicstudy of -HCG, oestradiol and progesterone was performed followingthe second treatment cycle only. Ovarian stimulation using aconstant dose of 75 IU of LH and increasing doses of FSH upto 225 IU, resulted in normal follicular growth and hormonalmilieu. Both women showed normal luteal phase oestradiol andprogesterone production and both women conceived following thesecond treatment cycle     

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.     

Effects of pineal indoles on ovarian response to gonadotropin-induced ovulation in mice

Summary Ovulation was induced in immature mice by injections of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG) spaced 48 hours apart. The mice were divided into six groups: one group received intraperitoneal injections of normal saline, another group received alcoholic saline which was used as the vehicle of pineal indoles, and the remaining groups received respectively hydroxyindoleacetic acid (HIAA), melatonin (MEL), methoxytryptamine (MTA) and methoxytryptophol (MTP). The pineal indoles were administered 24 hours before, on the same day as, 24 hours after and 48 hours after the PMSG injection. The mice were sacrificed 24 hours after the HCG injection. The numbers of growing primary follicles, multilaminar primary follicles, Graafian follicles, preovulatory follicles and corpora lutea in the ovary were not altered by treatment with pineal indoles. However, there was an increased incidence of follicular atresia in the groups treated with MEL, MTA and MTP. The pineal indoles did not affect the number of ovulated oocytes, but there was a large number of degenerated and fragmented ovulated oocytes in the MTA- and MTP-treated groups. Treatment with MEL, MTA and MTP also resulted in lower plasma levels of estradiol-17 and progesterone.     

Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: rationale, results, reflections and refinements

Low-dose follicle stimulating hormone (FSH) regimens for induction of ovulation for women with polycystic ovaries have succeeded in reducing the rate of ovarian hyperstimulation syndrome (OHSS) almost to nil and the rate of multiple pregnancies to a minimum of 6%. This has been achieved by reaching, but not exceeding, the threshold level of FSH, starting with a daily dose of 75 IU for 14 days, using small incremental dose rises where necessary, and inducing uniovulation in 70% of cycles. Conception rates are as good, if not better, than those achieved with conventional therapy. The miscarriage rate is still relatively high (20-25%) and obese women fare worse. Serum oestradiol concentrations and the number of large and intermediate follicles on the day of human chorionic gonadotrophin administration are much lower, in parallel with lower serum FSH concentrations. Inhibin values increase with the rise in serum FSH concentrations but those of luteinizing hormone decrease steadily throughout the follicular phase. New data using recombinant hFSH (rhFSH), rather than urinary gonadotrophin as the ovarian stimulant, demonstrate that treatment time is shortened. However, the ideal regimen has still to be formulated.     

输卵管切除术对超排卵的影响

目的:探讨单侧输卵管切除,切除侧卵巢对超排卵的反应性。方法:以因输卵管妊娠行单侧输卵管切除后不孕接受IVF-ET治疗的患者45例共52个周期为研究组,并以同期因输卵管阻塞(无输卵管积水)不孕行IVF-ET治疗的患者875例共913个周期为对照,分析输卵管切除侧卵巢与对侧卵巢对超排卵的反应性。结果:①两组的促性腺激素(Gn)用量、用药天数、hCG日E_2水平、卵裂率、平均移植胚胎数、种植率、临床妊娠率、流产率、异位妊娠率差异无统计学意义(P>0.05)。但单侧输卵管切除组的获卵数减少,差异有统计学意义(P<0.05)。②研究组卵泡晚期(注射hCG日)两侧卵巢大小(分别为35.1±6.5mm、38.2±5.9 mm)有差异,P<0.05。取卵日两组卵泡数(个)分别为6.7±4.5、8.6±3.3(P<0.05),回收卵子数(个)分别为4.9±3.7、6.4±3.6,P<0.05。结论:单侧输卵管切除者切除侧卵巢在行超排卵时,其卵泡晚期(注射hCG日)卵巢较小,取卵日的卵泡数和回收卵子数明显减少,手术可能影响卵巢的血液供应和超排卵效果。     

辅助生殖技术与多胎妊娠的关系及减胎术

辅助生殖技术(又称助孕技术)的发展在治疗不孕的同时导致多胎妊娠率的提高。本文阐述助孕技术与多胎妊娠的关系,以及如何通过严格控制超促排卵指征、控制移植胚胎数量、冻存胚胎、选择性单胚胎移植、减胎术的应用等方法来获得最佳妊娠率,同时降低助孕术后的多胎妊娠特别是三胎及三胎以上妊娠的发生。     

Effects of ovulation induction on ovarian morphology: an animal study

OBJECTIVE: The aim of this study was to investigate whether the ovulation induction has relation with postneoplastic lesions. MATERIALS AND METHODS: Seventy-eight female, 90-day-old rats were enrolled for the trial. They were divided into three groups. In the first group, 13 rats received one cycle of ovulation induction with Follitropin Beta and human chorionic gonadotropin. The second group of 13 rats received three cycles of ovulation induction, and the third study group consisted of 13 rats which received six cycles of ovulation induction. Each group had a control group consisting of same number of rats that had not received ovulation induction. At the 12th month after the ovulation induction protocols ended, rat ovaries were extirpated for histopathological examination. In histopathological examination, malignant lesions, ovarian cyst and cyst diameter, epithelial stratification, epithelial tufting, mitotic index, polymorphism of epithelial cells and nucleus, epithelial cell nuclear diameter, chromatin density nuclear atypia, and mitotic activity in ovarian cyst epithelium were evaluated. RESULTS: No malignant ovarian lesion was found in the three groups. Ovarian cyst development was most frequent in the rats that underwent six cycles of ovulation induction. Epithelial stratification and tufting were most frequent in the rats which underwent ovulation induction six times. Significant difference was found between induction and control groups in second and third groups for cellular and nuclear polymorphism, presence of nucleolus, and nuclear chromatin density. CONCLUSIONS: Although development of malignant lesion were not found in any of the rat ovaries after ovulation induction, increase in the prevalence of epithelial dysplasia especially with increase in the number of induction cycles shows that some ovarian pathologies can occur subsequent to ovulation induction.     

德生丹治疗排卵障碍性不孕症肾虚肝郁证患者临床研究

目的?观察中原门氏验方德生丹对排卵障碍性不孕症肾虚肝郁证患者的临床疗效。方法?将120例排卵障碍性不孕症肾虚肝郁证患者随机分为中药组（采用中药德生丹）、联合组（采用中药德生丹+克罗米芬）、西药组（单纯使用克罗米芬）。治疗12周后观察3组患者优势卵泡直径、子宫内膜厚度、宫颈黏液（Insler）评分及排卵率、妊娠率及血清雌二醇（E₂）、孕酮（P）水平的变化等。结果?治疗后3组优势卵泡直径与治疗前比较均显著增长（P<0.05~0.01）,联合组与西药组优于中药组（P<0.01）;3组中医证候积分均显著下降（P<0.01）,联合组与中药组优于西药组（P<0.01）;中药组、联合组子宫内膜厚度、Insle评分均有所增加（P<0.01）,优于西药组（P<0.05~0.01）;排卵日3组血清E₂水平均有所增长（P<0.01）,联合组与中药组优于西药组（P<0.05）;中药组、联合组黄体期血清P水平增长明显（P<0.01）,优于西药组（P<0.05~0.01）;3组排卵率比较,联合组与西药组均优于纯中药组（P<0.05~0.01）;3组妊娠率比较,联合组优于中药组、西药组（P<0.05~0.01）,中药组优于西药组（P<0.05）。结论?德生丹能改善排卵障碍性不孕症肾虚肝郁证患者临床症状,减少单纯克罗米芬抑制子宫内膜的不良作用,提高临床排卵及妊娠率。