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Duration of ovulation suppression with subcutaneous silicone implants containing norgestomet in Bos indicus heifers and cows.

The aim of this study is to determine the duration of suppressing oestrus or ovulation in Bos indicus heifers and cows using norgestomet (N) incorporated into a silicone implant. Twelve heifers and 18 cows undergoing oestrous cycles were allocated to one of two treatment groups (6 heifers and 9 cows per group). Animals were treated with a single subcutaneous (s.c.) silicone implant containing 3 mg of N or two identical silicone implants (6 mg of N in two silicone implants) on day 0 of the study. An analogue of prostaglandin F2-alpha was administered intramuscularly, to all animals on days 0 and 6 to induce regression of corpora lutea. Implants were removed from all animals on day 21. Animals were observed for signs of behavioural oestrus while implants were in situ and for 6 d following implant removal. Blood samples were collected on alternate days from day 0 to 20 and again on day 21 and analysed for plasma progesterone (P4). Transrectal ultrasonography was performed on days 0, 6, 10, 14, 18, 21, 24, 26,27, and along with concentration of P4 in plasma was used to confirm ovulation during the treatment period. The cumulative percentages of animals ovulating during the 21 days implants were in situ were 6.7% (3 mg of N in one silicone implant) and 0% (6 mg of N in two silicone implants)Intervals from implant removal to oestrus (mean +/- S.E.M.) did not differ significantly among animals treated with either 3 or 6 mg of N in silicone implants (46.8 +/- 7.0 vs. 55.4 +/- 7.1 h, P = 0.398). Variances in interval from implant removal to oestrus among animals treated with 3 or 6 mg of N in silicone implants were also homogeneous (P = 0.942). The mean diameter of the ovulatory follicle on day 21 was larger in the animals treated with 3 mg of N compared to animals treated with 6 mg of N in two silicone implants ( 13.1 +/- 0.8 vs. 9.7 +/- 0.7 mm, P = 0.005). We conclude that treatment with 3 mg of N in a silicone implant will suppress ovulation in Bos indicus heifers and most cows for 21 d. Six mg of N in two silicone implants will suppress ovulation for 21 d in both cows and heifers.

Animals↗

Blockade of ovulation in the rat by systemic and ovarian intrabursal administration of the fungicide sodium dimethyldithiocarbamate.

Dithiocarbamates, acting as inhibitors of catecholamine synthesis, have been reported to block ovulation in female rats following systemic administration by suppressing the neural noradrenergic signaling involved in triggering the ovulatory surge of luteinizing hormone. The ovaries also synthesize norepinephrine and receive noradrenergic input via sympathetic innervation, and it has been suggested that such input may play a role in follicular maturation and ovulation. The current experiments investigated whether the dithiocarbamate fungicide dimethyldithiocarbamate (DMDTC) would block oocyte release in normally cycling rats when administered systemically during the proestrous presurge period, and if so, would the compound also have a comparable direct ovarian effect on ovulation in response to a local intrabursal exposure of one ovary late on the day of vaginal proestrus. The results showed that a dose-related suppression of oocyte release was present in response to both intraperitoneal and intrabursal (IB) injections. But these effects appear to be mediated through different mechanisms. The unilateral IB injections were effective only on the exposed side for each ovarian pair, while no alterations were seen in ovarian norepinephrine. IB administration 24 h earlier blocked ovulation on both sides, while hCG injections were able to restore ovulation on the noninjected side only, implying that diestrous DMDTC was inhibiting the LH surge. The data indicate that while an effect on hypothalamic catecholamine synthesis may underlie the ovulatory blockade following intraperitoneal DMDTC administration, it does not appear to be involved in the response to local ovarian exposure. Moreover, the blockade in response to the diestrous IB exposure likely involves two separate mechanisms, one attributable to an alteration in ovarian hormonal feedback to the brain (or pituitary), inhibiting the LH surge, and the other associated with a direct, as yet undetermined, effect on local preovulatory events within the ovary.

Animals↗

Simple or repeated induction of superovulation: a study on ovulation rates and microvessel corrosion casts in ovaries of golden hamsters.

Repeatedly stimulated ovaries are reported to decrease the ovulation rate. One cause among others might be that the microvascular bed has been insufficiently developed. Therefore, 30-day-old golden hamsters were superovulated either once or repeatedly. At the light microscopic level, the ovulation rate in serially sectioned ovaries was indirectly determined by the occurrence of corpora lutea and of abnormal follicle rupture with oocyte release into the cortical stroma (IOR). For the study with scanning electron microscopy (SEM), the microvascular bed of the ovaries was cast with a polyester resin, and the corrosion casts of mature follicles observed. The histological sections of once-stimulated ovaries showed a large number of corpora lutea and IOR follicles. This indicated hyperovulation. In corrosion casts of once-stimulated ovaries, large-sized antral follicles with two layers of a dense capillary meshwork were observed. Capillary sprouts were aligned around the antrum 0 to 12 h after administration of human chorionic gonadotrophin (hCG), and these radiated towards the center of the antrum after 12 to 36 h had elapsed. The ovulation site was recognized at the follicle apex by three similarly sized structures which were either a sinusoid, an oocyte replica, or an opening. Repeatedly stimulated ovaries produced a low number of corpora lutea and almost no IOR follicles. This was judged as hypoovulation. The microvessels of mature follicles were reduced in number and incompletely cast. Widespread resin leakages were conspicuous in the follicle wall 36 h after hCG injection, but the capillary sprouts radiated towards the center of the antrum. No ovulation site was detectable. It is concluded, that capillary sprouts are induced before luteinization. The ovulation site is indicated by particular changes in its microvascular bed. An insufficiently developed microvascular bed may be responsible for hypoovulation in repeatedly stimulated ovaries.

Animals↗

Accidental hyperstimulation during ovulation induction.

Clinical hyperstimulation is the most serious complication of ovulation induction, occurring in approximately 3% of cases (0.8% in the severe form). Paradoxically, it seems to be rare following in vitro fertilization, probably because all the follicles are aspirated. High-risk patients are those with polycystic ovarian disease, hyperprolactinaemia and hypothyroidism. All forms of ovulation induction have been implicated. Use of LHRH agonists have not reduced the incidence of hyperstimulation and they may even have increased it. An ongoing pregnancy seems to predispose to the occurrence of hyperstimulation, due to the secretion of hCG. Clinically, three stages of hyperstimulation have been described by the WHO (mild, moderate and severe). The pathophysiology is not completely understood, although prostaglandins, histamines and, especially, the ovarian renin-angiotensin system may be involved. Local ovarian complications and thromboembolic complications have also occurred. The treatment of severe hyperstimulation is both symptomatic (fluid replacement, aspiration of effusions, moderate sodium and water restriction, small doses of diuretics) and specific (corticosteroids, aspiration of ovarian cysts, even voluntary interruption of pregnancy in the most serious forms). If the hyperstimulation occurs in the absence of pregnancy, antihistamines or antiprostaglandins can be given. Prevention is exceedingly important. This can be helped by recognition of polycystic ovarian disease and stimulation of these cases by clomiphene citrate or pure FSH associated, for use in in vitro fertilization, with prolonged desensitization using LHRH agonists. Daily ultrasound and hormonal monitoring of ovulation induction is required. When there is excessive response to stimulation, it is prudent not to induce ovulation with hCG or, alternatively, to aspirate all the follicles and freeze the embryos obtained without giving further injections of hCG in the luteal phase. Clinical ovarian hyperstimulation is the classic form of iatrogenic disorder and is the most important complication of ovulation induction treatments, since it can be life-threatening in its most severe form. In this chapter we review current knowledge concerning the frequency, factors associated with its occurrence, clinical aspects, physiopathological mechanisms and, finally, the possibilities for treatment and prevention.

Female↗

[Comparison of different protocols of ovulation induction, by GnRH agonists and chorionic gonadotropin].

OBJECTIVE: The aim of this study was to determine the best way of using a gonadotropin-releasing hormone agonist (GnRHa) for triggering ovulation and to analyse the reasons for short luteal phases. MATERIALS AND METHODS: Thirteen different regimens of GnRH-a administration were used to trigger ovulation using different dosages and either one, two or three administrations: triptorelin, buserelin spray, buserelin subcutaneously, leuprolide and nafarelin in 231 treatment cycles. Pregnancy rate and luteal phase duration were compared with those of a control group for whom ovulation was triggered with hCG. RESULTS: Ovulation with supraphysiologic elevation of both FSH and LH was achieved in the 13 GnRHa groups. For the five main groups analysed, GnRHa produced shorter and inadequate luteal phases than did hCG but no difference was found between agonists. Pregnancy rates were not statistically different between the agonist groups or in comparison with the hCG group. CONCLUSION: The use of GnRHa to trigger ovulation is efficient, despite short luteal phases, and has proven its utility in comparison with hCG. As the different modes of stimulation appear to yield comparable results, the cost of treatment should be a significant element to take into consideration.

Adult↗

Ovulation induction in women with polycystic ovary syndrome: randomized trial of clomiphene citrate versus low-dose recombinant FSH as first line therapy.

This single centre randomized controlled trial was undertaken to compare the efficacy and safety of clomiphene citrate and low-dose recombinant FSH as first line pharmacological therapy for anovulatory infertility associated with polycystic ovary syndrome (PCOS). Seventy-six infertile patients with PCOS were randomized to receive clomiphene citrate (50-150 mg/day for 5 days) (clomiphene citrate group, n = 38) or recombinant human FSH (FSH group, n = 38) in a chronic, low-dose, step-up protocol (daily starting dose 75 IU) for up to three consecutive cycles. Ovarian response was monitored by transvaginal ultrasonography and human chorionic gonadotrophin (HCG) was given to trigger ovulation in all cycles with appropriate follicular development. The primary outcome measure was cumulative pregnancy after undergoing up to three treatment cycles. Secondary outcomes were cycle cancellation rate, ovulation rate per cycle, cumulative ovulation rate, pregnancy rate per cycle, incidence of OHSS, cumulative live birth rate, and multiple birth rate. One hundred and four clomiphene citrate cycles and 91 FSH cycles were evaluable. The relative risk and its 95% confidence interval were 1.17 (0.97-1.46) for HCG cycles with ovulation, 1.78 (0.92-3.54) for the pregnancy rate per woman, and 1.83 (0.79-4.40) for live births per woman in favour of FSH. The cumulative pregnancy rate after three treatment cycles was 43% with FSH and 24% with clomiphene citrate (P = 0.06). By logistic regression analysis, the factors predicting ovulation included female age, serum androstenedione and use of FSH. Predictors of pregnancy were duration of infertility and use of FSH. This randomized controlled trial suggests that low-dose recombinant FSH may be an effective alternative to clomiphene citrate in first-line treatment for anovulatory PCOS patients. Thus, further studies, possibly multi-centre, in order to avoid problems with patient recruitment, are warranted to confirm these results.

Adult↗

Coitus-induced ovulation and its implications for estimates of some reproductive parameters.

It is estimated here that, at the time of conception, the mean coital rate of young women who subsequently bear DZ twins is about 6% higher than that of the general population of young married women. This differential seems too small to account wholly for the greater promptness in conceiving DZ twins. Accordingly, it is suggested that coital rate is associated with DZ twinning in two ways. The major link seems to be indirect and mediated by erotic response which causes an increase in gonadotrophin levels and thus in double ovulation. In a minority of cases, frequent coitus may give rise to DZ twins via superfecundation, but it seems that, in human beings, the corpus luteum of one ovum will usually inhibit fertilization of any further ova after a short interval. The evidence presented here, though indirect, seems to suggest that, under particularly erotic conditions, double ovulation is sometimes induced. It seems reasonable to infer that coitus also occasionally provokes or accelerates single ovulations, thus impugning some rhythm methods of contraception. But there seems no very good evidence that rape induces ovulation. Some notes are added on the implications of induced ovulation for estimates of fecundability and of the length of the fertile period.

Adult↗

Anti-macrophage inhibitory factor antibody inhibits PMSG-hCG-induced follicular growth and ovulation in mice.

PURPOSE: To investigate the effect of an anti-MIF antibody on PMSG-hCG-induced murine follicular growth and ovulation and to determine whether MIF plays an essential role in this process. METHODS: Mice were primed with an intraperitoneal injection of pregnant mare serum gonadotropin (PMSG) and were treated with an anti-rat MIF antibody and human chorionic gonadotropin (hCG) to induce ovulation. After that, the ovulated ova were counted. The ovaries were studied using standard histological procedures. RESULTS: Ovaries treated with the anti-MIF antibody showed reduced numbers of growing follicles surrounded by granulosa cells and theca cells with a little proliferation compared with the control. The average numbers of ova collected from mice treated with the anti-MIF antibody were reduced compared with those collected from control mice. CONCLUSIONS: Anti-MIF antibody inhibits the follicular growth and ovulation in mice, and MIF may play an important role in the inflammatory reactions during follicle growth and ovulation.

Animals↗

Successful ovulation induction, conception, and normal delivery after chronic therapy with etanercept: a recombinant fusion anti-cytokine treatment for rheumatoid arthritis.

Etanercept (Enbrel; Wyeth-Ayerst/Immunex Inc, Seattle, WA, USA) is a subcutaneously administered novel fusion protein consisting of the extracellular ligand-binding domain of the 75 kD receptor for tumor necrosis factor-alpha (anti-TNFalpha) and the Fc portion of human IgG1. The agent is synthesized by plasmid transfection of a Chinese hamster ovary cell line, utilizing recombinant DNA technology. Etanercept was approved by the US FDA for treatment of multi-drug resistant rheumatoid arthritis in 1998, but no human data exist regarding the impact of anti-TNFalpha therapy on human reproductive function or its use before ovulation induction. As TNFalpha potentiates collagenolysis via matrix metalloproteinase gene expression (thereby facilitating ovulation), there exists a theoretical risk that TNFalpha-inhibition could exert an undesirable effect on ovulation and pregnancy. In this report, we describe the first case of ovulation induction, intrauterine insemination, normal pregnancy and singleton delivery of a healthy infant following chronic ( > 1 year) pre-ovulatory TNFalpha-inhibitor therapy for rheumatoid arthritis. Reproductive endocrinologists and obstetrician-gynecologists should be familiar with etanercept therapy in the context of severe rheumatic disease, and offer appropriate reassurance regarding its safe use for infertility patients planning ovulation induction.

Adult↗

Energy balance and ovulation: small cages versus natural habitats.

In the laboratory, ovulation is suppressed when a mammal is in negative energy balance whether that state is caused by inadequate food intake, excessive locomotor activity or heavy thermoregulatory costs. In this paper, knowledge generated in the laboratory about the link between ovulation and energy balance is examined in relation to the kinds of energetic challenges mammals actually face in natural habitats. When viewed in that context, several conclusions can be drawn. First, females ovulate whenever extant energetic conditions permit unless the process is blocked by non-metabolic stress, social cues or a predictive seasonal cue such as photoperiod. In the latter case, most mammals show at least a seasonal tendency in their reproduction and the majority do not use a predictive cue; they reproduce opportunistically in relation to seasonal variation in the energetic characteristics of their environment. Second, the widely held assumption that a female's fat reserves must exceed a critical level in order that she may ovulate finds no support in the literature dealing with natural populations. Third, the surprisingly rapid responsiveness of the gonadotrophin releasing hormone (GnRH) pulse generator to energetic manipulation probably reflects the study of animals that are in a pure survival mode. Fourth, the complexity of the energetic challenges mammals face in the wild suggests that there are probably multiple metabolic and neural pathways coupling ovulation to energy balance and that these pathways are probably characterized by considerable overlap and redundancy. Thus, fifth, to develop a more realistic overview of these pathways there is a need for experimental designs that present mammals with the kinds of complex challenges they actually face in the wild habitats in which they evolved.

Adipose Tissue↗

Dietary protein intake during the oestrous cycle does not alter the ovulation rate in gilts.

The effect of protein intake on ovulation rate was investigated in cross-bred gilts. On Day 14 of the third oestrous cycle, luteolysis was induced by injection of an analogue of prostaglandin F(2alpha). The ovulation rate was recorded when gilts were killed on Day 27. In the first experiment, nutritional treatment was applied from Day 14 to Day 27. Gilts were fed diets providing the same amount of digestible energy, but containing either a low, medium or high amount of dietary protein. Protein restriction linearly decreased plasma concentrations of urea (P < 0.001) and had no effect on plasma concentrations of insulin-like growth factor-I and leptin measured at Day 27 (P > 0.1). Protein restriction did not influence ovulation rate (mean (+/- s.e.m.) 17.0 +/- 0.4; P > 0.1). In the second experiment, the nutritional treatment was applied from Day 5 until Day 27. Gilts received the same amount of digestible energy and either a low or a high amount of protein, as in Experiment 1. A third group of gilts received the high amount of protein and also more digestible energy. The ovulation rate did not differ between the three groups of gilts. These data indicate no effect of short-term dietary protein restriction on ovulation rate in cyclic gilts.

Animals↗

Oestrous behaviour and development of preovulatory follicles in goats induced to ovulate using the male effect with and without progesterone priming.

The objective of the current study was to examine follicular dynamics in goats induced to ovulate by using the male effect with or without progesterone pretreatment. Ten Murcian-Granadina goats were treated with a single dose of 25 mg of progesterone in olive oil on the day of male effect induction (Day 0), whereas ten does remained untreated. Changes in the ovarian follicular population and onset of oestrous behaviour were checked daily from Day 0 to the day on which ovulation was detected by ultrasonography. All of the treated goats and only 20% of control goats (P < 0.001) showed oestrous behaviour between 72 and 96 h after the introduction of bucks. Differences in follicle growth were found between the groups. The control goats exhibiting oestrous behaviour during the first 4 days of ovarian screening and all of the goats treated with progesterone had their preovulatory follicles in growing phase. However, the largest follicles in control does not showing oestrus in these first 4 days were in regressing phase, being necessary for the emergence of new preovulatory follicles from a new follicular wave between Days 6 and 7, for exhibition of oestrous behaviour and subsequent ovulation. In conclusion, the appearance of short luteal phases and delayed ovulation in goats treated with the male effect during seasonal anoestrous depends on the stage of follicle development at the time of buck introduction. A single injection of progesterone stimulates the emergence of a new follicular wave, able to grow and give adequate ovulation after induction of the male effect.

Animals↗

Lupins and energy-yielding nutrients in ewes. II. Responses in ovulation rate in ewes to increased availability of glucose, acetate and amino acids.

An experiment, using a total of 320 Merino ewes, over two successive breeding seasons was conducted to investigate the separate effects of energy-yielding and protein-yielding nutrients on ovulation rate in sheep. The available energy-yielding or protein-yielding nutrients in the blood of sheep fed a maintenance pelleted ration were increased by either intravenous infusions of metabolites (acetate, glucose or acetate + glucose), feeding lupin grain, modification of the pattern of rumen fermentation to increase propionate production using the ionophore, lasalocid, or by feeding of ruminally undegradable protein (formaldehyde-treated casein). All treatments were given for 9 days prior to and including expected time of ovulation. Ovulation rates were measured by laparoscopy. In the first season (the 1984 experiment) when the effects of lupin grain, glucose + acetate and formaldehyde-treated casein were compared, ovulation rates were increased significantly in the group fed lupin (29%, P less than 0.001) and the group infused with glucose + acetate (24%, P less than 0.01). There was an apparent (17%) but statistically non-significant increase in the group fed casein. In comparisons between lupin grain, glucose, acetate, glucose + acetate, formaldehyde-treated casein and lasalocid in the 1985 experiment there were similar significant increases in ovulation rates in the groups fed lupin, and those infused with glucose or glucose + acetate (approximately 25%, P less than 0.001). The increase in the group infused with acetate was lower at 14% (P less than 0.05) and the increases of 7% in the groups fed casein or lasalocid were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Stimulation of LH release and ovulation in the rat by cutaneous application of luteinizing hormone-releasing hormone (LH-RH) in dimethyl sulfoxide (DMSO).

The efficacy of cutaneously applied luteinizing hormone releasing hormone (LH-RH) in stimulating LH release in the chronically ovariectomized, estrogen/progesterone-blocked rat and ovulation in the chlorpromazine-blocked, proestrous rat was investigated. Following the cutaneous application of 25 or 100 mug of LH-RH in 100% dimethyl sulfoxide (DMSO), serum LH rose to a peak at 1 hr, then declined toward basal levels in the ensuing 3 to 4 hr. LH-RH applied cutaneously in either 100% DMSO or 0.9% NaCl was also capable of inducing ovulation in the chlorpromazine-blocked, proestrous rat; however, LH-RH in 0.9% NaCl did not yield a linear log-dose-response relationship, therefore a valid ED50 potency ratio for DMSO/0.9% NaCl could not be estimated. Nonetheless, 0.9% NaCl was a considerably less effective cutaneous vehicle than DMSO. Cutaneous application of LH-RH in DMSO in doses of 100, 50, 25, 10, 5, 2.5 and 1 mug induced ovulation in 100%, 100%, 90%, 73%, 30%, 10% and 0% of the rats, respectively. When the percent ovulation response was transformed to probits and plotted against the logarithm of the LH-RH dose an approximately linear log dose-response was obtained; the same relationship also held true for ovulation induction following sc LH-RH administration. In turn, the ED50's of these two parallel dose-response curves yielded a potency ratio estimate (sc/cutaneous) of 0.025, suggesting that 2.5% of the cutaneously applied LH-RH dose was absorbed through the skin in a biologically active form. These data indicate that DMSO privdes a convenient cutaneous vehicle for the administration of LH-RH.

Administration, Topical↗

Combined ethinylestradiol/gestodene contraceptive patch: two-center, open-label study of ovulation inhibition, acceptability and safety over two cycles in female volunteers.

OBJECTIVES: Determination of the ovulation inhibition efficacy of a new, transparent, transdermal, combined hormonal contraceptive patch (area 10 cm2) containing 0.9 mg ethinylestradiol and 1.9 mg gestodene in an open-label study of healthy, female volunteers (aged 18-35 years). METHODS: A total of 199 volunteers from two centers were requested to use the contraceptive patch (one patch/week for 3 weeks, followed by 1 week of no treatment), throughout two menstrual cycles. Ovarian activity was monitored by transvaginal ultrasonography and serum hormone determinations, and classified according to the Hoogland score. RESULTS: Ovulation inhibition was achieved in all participants (Hoogland score < 6). Secondary efficacy measures, including suppression of serum concentrations of estradiol and progesterone, and of the mid-cycle luteinizing hormone surge, confirmed ovulation inhibition. Ovulation returned in 85.7% of participants during the first cycle after cessation of treatment. There were no abnormal changes in safety parameters. A large majority of users rated the contraceptive patch as 'very convenient'. CONCLUSIONS: This study showed that the new, combined ethinylestradiol/gestodene contraceptive patch was highly effective in reversibly inhibiting ovulation, well tolerated and regarded as 'very convenient' by the majority of users. This new, transparent, transdermal matrix patch is an attractive alternative form of contraception.

Administration, Cutaneous↗

Mouse major urinary proteins trigger ovulation via the vomeronasal organ.

The major urinary proteins are a species-specific complex of proteins excreted by male mice that influence the reproductive behavior and the neuroendocrine condition of female mice through the olfactory system. The aim of this work is to determine their influence on ovulation. The major urinary proteins isolated from the urine of adult male mice were voided of bound odorants, dissolved at a physiological concentration in urine of prepubertal mice, and put on the nostril of reproductively cycling female mice housed in groups, the first day of estrus at 1100. The eggs shed in the oviducts were counted under dissection the morning of the second day of estrus. The results showed that 1) a single stimulus of the major urinary proteins increased ovulation nearly as much as the whole urine of male mice, 2) the effect was not elicited by male rat urine which contains different proteins, 3) a peptide with four residues of the amino-terminal sequence of the major urinary proteins stimulated ovulation, and 4) mice that had been isolated or had the vomeronasal organ (VNO) removed did not respond to the major urinary proteins and had a high spontaneous ovulation. The results suggest that the major urinary proteins activate the neuroendocrine system through the VNO and trigger ovulation.

Animals↗

Prolactin delays gonadotrophin-induced ovulation and down-regulates expression of plasminogen-activator system in ovary.

This study was conducted to determine whether prolactin (PRL) suppresses gonadotrophin-induced ovulation and disturbs the co-ordinated gene expression of tissue type plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAI-1) in rat ovary. Immature female rats were injected with 10 IU pregnant mare's serum gonadotrophin to stimulate follicle growth, and 48 h received different doses of prolactin followed by 7 IU human chorionic gonadotrophin (HCG). The oviducts were examined for the presence of ova, and the amounts of tPA and PAI-1 mRNA present in the ovary were measured at various times after the hormone treatment. PRL had no significant effect on ovarian weight but caused a dose-dependent decrease in ovulation number. In the control animals receiving HCG alone, 13.3 +/- 1.3 (mean +/- SEM) ova/oviduct were found; while in animals receiving HCG plus 50, 100 or 200 microg PRL, the ovulation number was dose-dependently suppressed by 53.6, 66.9 and 76% respectively at 18 h after treatment. PRL suppression of HCG-induced ovulation was time-dependent. By 24 h after treatment, the number of ova in the oviducts in HCG- and HCG plus PRL-treated groups was not significantly different. PRL also suppressed HCG-induced tPA gene expression in a dose- and time-dependent manner. At all time points examined, tPA mRNA content of whole ovaries and granulosa cells (GC) in PRL-treated groups was lower than in the HCG-treated controls. The activities of PAI-1 in ovarian extracellular fluid (OEF) and PAI-1 mRNA in the theca-interstitial cells (TI) in the PRL-treated groups were higher than in the HCG-treated controls. The highest stimulation by PRL of PAI-1 activity in OEF and of PAI-1 mRNA in TI was observed at 9 h and 6 h after HCG treatment respectively. The localization of tPA and PAI-1 antigens in the ovaries was consistent with changes in the mRNA and activity levels. These data suggest that PRL temporarily delays, but does not completely inhibit, HCG-induced ovulation, which may be caused by a suppression of PA-mediated proteolysis.

Animals↗

Histological evaluation of endometrium on the day of oocyte retrieval after gonadotrophin-releasing hormone agonist-follicle stimulating hormone ovulation induction for in-vitro fertilization.

The objective of this study was to evaluate the histopathological characteristics of endometrial biopsies taken on the day of oocyte recovery in in-vitro fertilization (IVF) cycles with a satisfactory response to ovulation induction. A group of 33 patients who went through ovulation induction for IVF, and in whom an endometrial polyp was suspected on transvaginal ultrasonography during the monitoring phase, were studied. Following oocyte recovery, hysteroscopy, polypectomy and endometrial curettage were performed. Dating of endometrial glands and stroma was carried out in the tissue not containing the polyps. The total dose of follicle stimulating hormone (FSH), duration of ovulation induction, peak oestradiol and luteinizing hormone (LH) concentrations, thickness of endometrium and number of oocytes were recorded and compared to the endometrial dating of the specimens. In 15 cycles (45.5%), the endometrium was classified as 'in phase' (group I), 'advanced' by 2-4 days in a further 15 (45.5%, group II), and in the remaining three cycles (9%) it was delayed in maturation (group III). Younger age was correlated with advanced staging of the endometrium (r = -0.42; P = 0.015). Women with 'in phase' and 'advanced' maturation were similar in their response to ovulation induction; however, there was a strong correlation between advanced dating of endometrium and number of oocytes retrieved (r = 0.49; P = 0.04). Endometrial staging on the day of oocyte retrieval varied widely in patients treated by the same gonadotrophin-releasing hormone agonist (GnRHa)/FSH protocol for ovulation induction. This difference was not predictable by parameters monitored through the cycles.

Adult↗