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PubMed1997

Asymmetrical effects of the unilateral implant of pilocarpine on the preoptic-anterior hypothalamic area on spontaneous ovulation of the adult rat.

The effects on ovulation at the next estrus after unilaterally implanting pilocarpine in the preoptic-anterior hypothalamic area (POA-AHA) of rats on each day of the estrous cycle were analyzed. Implantation on the left side of POA-AHA on the day of estrus blocked ovulation in all animals, whereas implantation on the right side did not (0/5 vs. 4/4, P < 0.05). Implantation on diestrus 1 or 2 on either side of the POA-AHA blocked ovulation. Implantation on the right side of the POA-AHA at the day of proestrus blocked ovulation (1/6 animals ovulated), while 10/12 with pilocarpine on the left side ovulated (P < 0.05). The administration of 3.7 micrograms of GnRH at 13:00 h on the expected day of proestrus induced ovulation in 36/42 treated animals. In rats with a pilocarpine implant, the injection of estradiol benzoate on diestrus 2 restored ovulation only in those animals with the pilocarpine implant placed in the left side of the POA-AHA, performed on the day of estrus. The results support the previous statements that in the adult rat POA-AHA, the cholinergic mechanism regulating preovulatory GnRH release, is lateralized. In addition, at the beginning of the estrous phase, the POA-AHA-cholinergic system needs to remain undisturbed for normal ovulation to take place at the next estrus.

Animals↗
PubMed1986

Timing of the onset and duration of ovulation in superovulated beef heifers.

Thirty-two beef heifers were induced to superovulate by the administration of follicle stimulating hormone-porcine (FSH-P). All heifers received 32 mg FSH-P (total dose) which was injected twice daily in decreasing amounts for 4 d commencing on Days 8 to 10 of the estrous cycle. Cloprostenol was administered at 60 and 72 h after the first injection of FSH-P. Heifers were observed for estrus every 6 h and were slaughtered at known times between 48 to 100 h after the first cloprostenol treatment. The populations of ovulated and nonovulated follicles in the ovaries were quantified immediately after slaughter. Blood samples were taken at 2-h intervals from six heifers from 24 h after cloprostenol treatment until slaughter and the plasma was assayed for luteinizing hormone (LH) concentrations. The interval from cloprostenol injection to the onset of estrus was 41.3 +/- 1.25 h (n = 20). The interval from cloprostenol injection to the preovulatory peak of LH was 43.3 +/- 1.69 h (n = 6). No ovulations were observed in animals slaughtered prior to 64.5 h after cloprostenol (n = 12). After 64.5 h, ovulation had commenced in all animals except in one animal slaughtered at 65.5 h. The ovulation rate varied from 4 to 50 ovulations. Approximately 80% of large follicles (> 10 mm diameter) had ovulated within 12 h of the onset of ovulation. Onset of ovulation was followed by a dramatic decrease in the number of large follicles (> 10 mm) and an increase in the number of small follicles (</= 5 mm). These data indicate that ovulations in superovulated beef heifers occur over 12 h and commence approximately 24 h after the onset of estrus and 22 h after the peak of LH.

Journal Article↗
PubMed1989

Temporal relationships among estrus, body temperature, milk yield, progesterone and luteinizing hormone levels, and ovulation in dairy cows.

Estrous cycles of 10 postpartum cyclic Holstein cows were synchronized using prostaglandin f(2alpha) (PGF(2alpha)) given twice 12 d apart to study the relationship of the onset of estrus, body temperature, milk yield, luteinizing hormone (LH) and progesterone concentration to ovulation. Blood samples and body temperatures (vaginal and rectal) were taken every 4 h until ovulation, starting 4 h prior to the second PGF(2alpha) treatment. All cows were observed for estrus following the second administration of PGF(2alpha). Ultrasound scanning of the ovaries commenced at standing estrus and thereafter every 2 h until the disappearance of the fluid filled preovulatory follicle (ovulation). Two cows failed to ovulate and became cystic following the second PGF(2alpha) treatment. The remaining eight cows exhibited a decline in progesterone to <1.0 ng/ml within 28 h, standing estrus and a measurable rise (> 1.0 degrees C) in vaginal but not rectal temperature, and ovulated 90 +/- 10 h after the second PGF(2alpha) treatment. Onset of standing estrus, LH peak and vaginal temperature were highly correlated (P<0.05) with time of ovulation (0.82, 0.81 and 0.74, respectively). Intervals to ovulation tended to depend upon parity. Pluriparous (n = 4) and biparous (n = 4) cows ovulated within 24 and 30 +/- 3 h from the onset of standing estrus; 22 and 31 +/- 2 h from the LH peak; and 22 and 27 +/- 3 h from peak vaginal temperature (mean +/- standard error of the mean), respectively. The results indicated that the onset of standing estrus and rise in vaginal temperature are good practical parameters for predicting ovulation time in dairy cattle.

Journal Article↗
PubMed1994

Effect of dose of GnRH analog on ovulation in mares.

Proper timing of insemination for optimal conception is accomplished by frequent palpations per rectum, by ultrasonography of the preovulatory follicle and/or by treatment with hCG or GnRH. Sustained release of GnRH from implants has been shown to hasten ovulation. Therefore, 2 studies were conducted to evaluate the efficacy of a GnRH analog, deslorelin, for hastening ovulation in nonlactating cyclic mares. The GnRH implant was 2.3x3.7 mm and released deslorelin for 2 to 3 days. In Experiment 1, 60 nonlactating, cycling mares were assigned to 1 of 5 doses: 0, 1.2, 1.7, 2.2 and 2.7 mg per implant. Mares were assigned sequentially on the first day of estrus (Day 1). Ovaries were examined per rectum and with ultrasonography every 12 h until ovulation. Once the mares obtained a follicle>30 mm, they were injected subcutaneously with a GnRH implant. The mares were inseminated every other day during estrus with semen from 1 of 3 stallions. Pregnancy was determined with ultrasonography. Experiment 2, 40 nonlactating, cyclic mares were assigned to 1 of 5 treatments (same treatments as in Experiment 1). Data were obtained on interval to ovulation, duration of estrus and pregnancy rates at 12, 18 and 35 d after ovulation. Time to ovulation was shorter (P<0.05) in GnRH-treated mares than in control mares in the Experiment 1. Mean time to ovulation was 68, 49, 48, 47, 44 h in Experiment 1, and 91, 66, 58, 46, 58 h in Experiment 2 for mares given 0, 1.2, 1.7, 2.2 and 2.7 mg/mare in the 2 trials. Averaged for both experiments, the proportion of mares ovulating within 48 h of treatment was 40, 75, 85, 90 and 90% for 0, 1.2, 1.7, 2.2 and 2.7 mg/mare. For both experiments, there was no effect of GnRH on pregnancy rate. In summary, a subcutaneous implant containing GnRH analog induced ovulation in most mares by 48 h of injection, and there was no advantage of doses higher than 2.2 mg/mare.

Journal Article↗
PubMed1977

Temperature-dependent Response to Indoleacetic Acid Is Altered by NH(4) in Cultured Cotton Ovules.

Unfertilized cotton ovules, cultured in vitro, produced fiber in response to indoleacetic acid (IAA) and/or gibberellic acid (GA(3)). Of the two hormones, IAA produced the greater amount of fiber per ovule, and the effect of both hormones applied simultaneously was approximately additive. Depending upon in vitro culture temperature, a variable number of unfertilized cotton ovules produced fiber in response to 5 mum IAA. The response to IAA was "all or none" for each ovule. The percentage of ovules responding to 5 mum IAA ranged from zero at 28 C to 100 at 34 C. The ability to respond at nonpermissive culture temperatures (i.e. 28 to 30 C) was markedly increased by including 2.5 mm NH(4)NO(3) in the KNO(3)-based medium or by increasing concentrations of IAA. The inclusion of NH(4) (+) in the basal culture medium provided only an increased percentage of ovules producing fiber in the presence of IAA, but did not increase fiber production per ovule. Temperature, like GA(3), increased both the number of ovules producing fiber in response to IAA and the amount of fiber produced per ovule.

Journal Article↗
PubMed1985

Photocontrol of Peanut (Arachis hypogaea L.) Embryo and Ovule Development in Vitro.

The purpose of the present study was to determine the nature of the photoreceptor that controls the light-dependent development of the peanut ovule and embryo, and to determine whether this photoreceptor activity is located in the ovular or the embryonic tissue. Peanut ovules were aseptically excised from surface sterilized gynophores (pegs) and cultured in darkness, continuous far red (FR), or given 15 minutes daily irradiations with white (W), red (R), blue (B); FR, R/FR, FR/R light for 21 days. Increases in the volume of ovules cultured in dark, continuous FR, FR, or R/FR were significantly greater than for ovules cultured in W, R, FR/R, or B radiation. Halving the ovule or removing the micropyle did not affect the relative change in ovule volume in response to different light treatments. When the light sources were altered after the first 10 days of culture, the ovules exposed first to darkness or FR radiation began to increase in ovule volume which then ceased after subsequent exposure to W, R, or B radiation. Likewise, if W, R, or B radiation was given during the first 10 days, ovule development was inhibited, and could be stimulated by exposure to darkness or FR light. Growth of embryos, when removed from the influence exerted by ovular tissue, was unaffected by the light. However, when embryos remained attached to the ovular tissue, their growth was stimulated in darkness or by FR light and inhibited by W, R, or B light. The R/FR reversibility indicates that the photoreceptor that regulates ovular growth is phytochrome and that the maternal ovular tissue appears to be the site of photoreception, which may then transmit some developmental signal to the embryo.

Journal Article↗
PubMed1988

Ultrasonic assessment of ovulation in cyclofenil induced ovulatory cycles.

Graafian follicle growth was studied by ultrasound scanning during the peri-ovulatory period in 64 ovulatory cycles in 32 infertile patients on cyclofenil treatment, and compared with a control group of 32 patients with confirmed ovulatory cycles assessed on the basis of serum progesterone levels in the middle of the second half of the cycle. The mean maximum diameters of the leading follicles before ovulation were 21.9 +/- 0.6 (S.E.) mm and 24.4 +/- 0.5 (S.E.) mm, respectively for the cyclofenil group and the normal control group (P greater than 0.05). In 79% of the cyclofenil stimulated group and 83% of the spontaneous ovulation group, ultrasonic evidence of ovulation was present between 12 and 36 h after the initial increase in urine LH levels. Ultrasound scanning was found to be simple, and a quick method of monitoring graafian follicle development and ovulation on cyclofenil therapy and the cycles were comparable to the spontaneous ovulatory cycles as assessed on the basis of graafian follicle diameter, and the time of ovulation. Cervical score was not found to be useful to assess ovulation time in the cyclofenil treated group since 31.3% achieved a score of 10 or more on day -4, 93.8% within 24 h of ovulation and 24% on day 3 following the ovulation.

Cresols↗
PubMed2006

A new era in ovulation induction.

OBJECTIVE: To evaluate the efficacy of aromatase inhibitors in ovulation induction, superovulation, and IVF. DESIGN: A literature search was conducted with the key words "aromatase inhibitor," "letrozole," "anastrazole," "ovulation induction," "ovulation," and "superovulation" in MEDLINE, EMBASE, and the Cochrane Database of systematic reviews. RESULT(S): Ovulation induction with letrozole is associated with an ovulation rate of 70%-84% and a pregnancy rate of 20%-27% per cycle. In one study, ovulation and pregnancy rates with letrozole seemed to be higher than those of anastrazole. In superovulation, letrozole is associated with few developing follicles and thick endometrium. The use of letrozole for superovulation is associated with a pregnancy rate higher than with the use of clomiphene citrate (CC) (16.7% vs. 5.6%). The addition of letrozole to FSH treatment leads to a decreased FSH requirement. The pregnancy rate for treatment with letrozole and FSH was similar to that for FSH alone. CONCLUSION(S): Aromatase inhibitors are as effective as or superior to CC in ovulation induction and in superovulation. Unlike CC, they do not carry an antiestrogenic effect on the endometrium. Given the advantages of aromatase inhibitors, they can be used to replace CC as ovulation-inducing drugs. Their role in IVF remains to be determined.

Aromatase Inhibitors↗
PubMed2006

Evaluation of methodology for administration of porcine FSH for use in estrus induction and for increasing ovulation rate in prepubertal gilts.

Ovulation rate influences production efficiency of oocytes and embryos and depends upon the amount of gonadotropin administered and the ratio of FSH:LH activity. In Experiment 1, gilts (n=135) were assigned to receive 10 or 15 Armour units (AU) of porcine FSH containing 6%, 10%, or 15% LH, whereas controls received PG600. Gilts received 1/6th the FSH dose in six sc administrations at 8-h intervals. There was no treatment effect on incidence of estrus (66%) or cysts (23.9%), or number of corpora lutea (CL, 29.6). However, treatment did affect the percentage of gilts ovulating (P<0.05) with fewer 10 AU FSH with 15% LH-treated gilts ovulating (15%) compared to controls (72%), whereas the other treatments did not differ (range, 44-65%). Experiment 2 tested whether FSH in polyvinlypyrrolidinone (PVP) could induce estrus and ovulation with reduced administration frequency. Gilts (n=105) were assigned to receive 15 AU FSH with 10% LH in one (1P) or two sc administrations (2P) whereas controls received PG600. There was no treatment effect on incidence of estrus (64%) or cysts (22%). However, the percentage of gilts ovulating was lower for 1P (56%), but did not differ (P<0.05) between 2P (83%) and controls (85%). Treatment influenced ovulation rate (P<0.05) with 2P having more CL (24) than controls (12) and 1P (19). Results indicated that 10 and 15 AU FSH induced estrus and ovulation, although high LH content proved detrimental. Further, 15 AU FSH with 10% LH in PVP allowed for reduced administration frequency without compromising ovulation.

Age Factors↗
PubMed1990

Evidence for the inhibitory effect of 5-hydroxytryptamine at central and peripheral sites on ovulation in rabbits.

1. The effect of 5-hydroxytryptamine (5-HT) has been investigated on ovulation per se as well as on induced ovulation in rabbits. 2. 5-HT administered intracerebroventricularly (i.c.v.) did not induce ovulation per se. 3. The ovulation was induced by coitus, subcutaneous administration of progesterone and intravenous administration of cupric acetate. 4. Postcoital and progesterone induced ovulation was found to be blocked by i.c.v. administered 5-HT. 5. Cupric acetate induced ovulation was, however, not found to be blocked by i.c.v. administered 5-HT. 6. Intraperitoneal administration of 5-HT was found to block cupric acetate induced ovulation. 7. It is concluded that 5-HT exerts an inhibitory control over ovulation by acting at central as well as at peripheral sites in rabbits.

Animals↗
PubMed1975

Ovulation in PMS-treated rats with gonadotropin releasing hormone after pentobarbital and melatonin block.

The immature rat that has been induced to ovulate with pregnant mare serum (PMS) has proven to be a valuable model for the study of antiovulatory compounds. This paper describes an extension of this model in order to attempt to study the site of action of substances such as pentobarbital and a pineal compound, melatonin. A first experiment was designed to define a specific time for injecting pentobarbital in order to inhibit ovulation. In this study immature female rats were given injections with 25 IU PMS; pentobarbital was given at various times after PMS treatment. This study showed that sodium pentobarbital (35 mg/kg, i.p.) inhibits LH release and ovulation when rats have been anesthetized between 2 and 6 p.m. on day 2 after PMS treatment. In a second experiment ovulation was blocked with pentobarbital (35 mg/kg, i.p., beginning at 12 noon and at 2 p.m. on day 2 after PMS treatment) and completely restored to normal with the s.c. injection of 2 mug GnRH at 2 and 4 p.m. on day 2 after PMS treatment. In the third experiment, varying doses of GnRH were studied for their capacity to overcome the pentobarbital block. This study showed that 2 mug, 1 mug, 500 ng, and 250 ng of GnRH at 2 and 4 p.m. on day 2 after PMS treatment were equipotent in causing ovulation. In a fourth experiment ovulation was blocked with melatonin and this block was overcome with exogenous GnRH. In the last study exogenous GnRH was shown to restore ovulation after being blocked by both melatonin and pentobarbital. This evidence suggests that pentobarbital and melatonin inhibit ovulation by inhibiting the secretion of endogenous GnRH.

Animals↗
PubMed2004

Passive immunoneutralization of endogenous inhibin increases ovulation rate in miniature Shiba goats.

We reported previously that passive immunization against inhibin enhances follicular growth and increases the ovulation rate. However, the ovulation rate was not comparable to the number of follicles. Therefore, the aim of this study was to attempt to increase the ovulation rate by increasing the interval between inhibin immunization and PGF2alpha injection. Five miniature Shiba goats were treated with 10 ml inhibin antiserum (inhibin-AS) developed against [Tyro30]-inhibin alpha (1-30). A control group (n=5) was treated with normal goat serum. All animals were injected intramuscularly with 125 microg PGF2alpha 72 h after treatment to induce estrus and ovulation. Blood samples were collected for hormonal assay and the ovulation rate was determined by laparotomy. In contrast to the control group, there was a significant increase in plasma concentrations of FSH in the immunized group. After luteolysis, plasma concentrations of estradiol-17beta increased markedly to a preovulatory peak about 2 folds higher (P<0.01) than that of controls. In addition, the ovulation rate was greater in the immunized group (14.4 +/- 2.2) than in the control group (2.2 +/- 0.6), and the mean number of follicles > or = 4 mm in diameter was 10.0 +/- 0.8 in the inhibin-AS group compared with 2.4 +/- 0.3 in control group. The present results demonstrate that immunoneutralization of endogenous inhibin increased FSH secretions in miniature shiba goats. The increased FSH secretion enhanced follicular growth and increased the ovulation rate. Additionally, increasing the interval between inhibin-AS and PGF2alpha injections (to 72 h) resulted in a greater ovulation rate compared with the previous protocol (48 h). Therefore, inhibin-AS treatment proved to be an effective alternative to exogenous gonadotropin methods for induction of superovulation in goats.

Animals↗
PubMed1990

Number of mature follicles ovulating after a challenge of human chorionic gonadotropin in different breeds of sheep at different physiological stages.

The ovulatory response of ewes from breeds that differ widely in prolificacy (Ile-de-France, ++ Booroola Merino, Romanov, F+ Booroola Merino and F+ Booroola Romanov with adult ovulation rates of about 1.5, 1.2, 3, 3 and 3.5 respectively) to 750 IU of hCG given at different physiological stages (before puberty, during anestrus or during the luteal phase) was compared. In all except one experiment, hCG induced ovulation in 73 to 98% of the lambs, indicating that follicles sensitive to LH were present at all stages studied. Ranking of the breeds according to hCG-induced ovulation rate in prepuberal lambs was similar to that based on adult ovulation rate. Furthermore, hCG induced more ovulations in prepuberal F+ than in ++ lambs (3.7 +/- 1.4 vs 1.7 +/- .8 at 4.5 mo of age) as well as in anestrous ewes (F + at 3.1 +/- 1.8 vs ++ at 1.6 +/- .7). Within ewes, the correlation between hCG-induced ovulation rate and mature ovulation rate was positive in nonprolific breeds but not significant in prolific breeds. We conclude that 1) the number of hCG-induced ovulations can be used to identify sheep that are carriers of the Booroola gene and 2) the mechanisms responsible for a number of large ovulatory follicles typical of a breed are present at stages (prepuberal, anestrus, luteal phase) other than the follicular phase.

Animals↗
PubMed2002

Oral versus injectable ovulation induction agents for unexplained subfertility.

BACKGROUND: Oral (anti-oestrogens) and injectable (gonadotrophins) ovulation induction agents have been used to increase the number of eggs produced by a woman per cycle in treatment for unexplained subfertility. It is unclear whether there are significant advantages of one type of treatment over the other in this context or in terms of fertility. OBJECTIVES: To assess the efficacy of oral versus injectable ovulation induction agents for unexplained subfertility. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of relevant randomised controlled trials. SELECTION CRITERIA: All trials where oral ovulation induction agents were compared with injectable ovulation induction agents in treatment groups generated by randomisation, from couples with unexplained subfertility, were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Five randomised controlled trials, including a total of 231 identified couples with unexplained subfertility, were found and included in this review. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth, miscarriage, multiple birth, occurrence of ovarian hyperstimulation syndrome and cycle cancellation. MAIN RESULTS: Where trials with important co-interventions were excluded, there was no significant difference in the odds of beneficial outcomes for oral versus injectable ovulation induction agents - live birth per couple (OR 0.06, 95%CI 0.00-1.15), pregnancy per woman (OR 0.33, 95%CI 0.09-1.20); nor of detrimental outcomes for injectable versus oral agents - miscarriage (OR 0.11, 95%CI 0.00-2.84); there were no reported cases of multiple births, cases of ovarian hyperstimulation or discontinued cycles consequent upon overstimulation. Where trials with the co-intervention of a human chorionic gonadotrophin trigger injection (given only in the injectable ovulation induction agent treatment arm) were not excluded there was no significant difference in the odds of live birth per couple (OR 0.40, 95%CI 0.15-1.08). However oral ovulation induction agents had significantly reduced odds of pregnancy per woman compared to injectable ovulation induction agents (OR 0.41, 95%CI 0.17-0.80). For detrimental outcomes, there were no significant differences in the odds of miscarriage (OR 0.61, 95%CI 0.09-4.01) and multiple birth (OR 1.08, 95%CI 0.16-7.03) for injectable versus oral agents. No data were available concerning the occurrence of ovarian hyperstimulation syndrome nor cycle cancellation. REVIEWER'S CONCLUSIONS: There is insufficient evidence to suggest that oral agents are inferior or superior to injectable agents in the treatment of unexplained subfertility. Information on harms is sketchy, and remains compatible with large differences in either direction. Much larger trials than have previously been undertaken are required to provide information on relative harms as well as benefits.

Administration, Oral↗
PubMed1989

Contraceptive potential of RU 486 by ovulation inhibition: I. Pituitary versus ovarian action with blockade of estrogen-induced endometrial proliferation.

In previous studies, RU 486 administration arrested spontaneous folliculogenesis. To investigate the central versus peripheral effects of RU 486 on the ovarian/menstrual cycle, including endometrial proliferation, RU 486 was administered daily (10 mg/kg/day, im) from menstrual cycle day 3 or 7 to day 25 in normal adult cynomolgus monkeys receiving hMG treatment (37.5 IU/day) from days 3-8 (n = 6). RU 486 administration with hMG/hCG therapy did not inhibit ovarian response, as evidenced by steroidogenesis and ovulation. Nine of 23 oocytes retrieved by lavage or follicular aspiration at laparotomy after ovulation induction were morphologically classified as mature preovulatory status. Whereas an endometrial biopsy performed on cycle day 25 in control monkeys revealed an in phase mature secretory endometrium, histologic sections from RU 486 plus hMG/hCG treated females uniformly demonstrated atrophic to weakly proliferative endometrium on cycle day 25, despite serum estradiol levels greater than 300 pg/ml. Three months after the initial 25-day study endometrial biopsies revealed persistent atrophic endometrium, even though repeated ovulation induction with hMG/hCG therapy elevated serum estrogen concentrations. The findings prevailed whether RU 486 treatment began on cycle day 3 or 7. The intermenstrual interval was significantly (P less than 0.01) lengthened by RU 486 treatments (28.5 +/- 2.0, control vs 131.3 +/- 11.5 days, RU 486). In summary, RU 486 consistently blocked ovulation unless hCG was provided and elicited a persistent retardation of early proliferative endometrium when administered daily beginning in early or mid-follicular phase. The normal mitogenic effects of elevated ovarian estrogen secretion on endometrial tissue were quelled, uniformly resulting in amenorrhea. The long-lasting action of RU 486, causing ovulation inhibition and atrophic endometrium, may be due to the depot effect of im injection. In addition, RU 486 did not prevent ovarian steroidogenesis, ovulation or oocyte maturation when an ovulation induction regimen of hMG/hCG was given. These findings show that RU 486 prevented ovulation by diminishing pituitary gonadotropin secretion, rather than by direct effects on ovarian folliculogenesis, and induced amenorrhea by inhibiting estrogen-induced endometrial proliferation.

Animals↗
PubMed1993

Inhibitory effect of mifepristone (RU 486) on ovulation in the isolated perfused rat ovary.

The antigestagen mifepristone (RU 486) acts by blocking the progesterone receptor. Mifepristone has been used clinically for medical termination of pregnancy. It has recently also been shown that it can be used as an effective contraceptive agent in many species including the human. This contraceptive effect is acquired through prolonged exposure to mifepristone during the follicular phase and has been linked to disrupted folliculogenesis and inhibition of the LH surge. In the present study it is tested if mifepristone inhibits ovulation by a direct action on the ovary at the time of the LH surge. Preovulatory rat ovaries from immature Sprague-Dawley rats primed with 20IU of equine CG were perfused in vitro for 20 h in the presence of LH and 3-isobutyl-1-methylxanthine (IBMX) to induce ovulations. Mifepristone was added to study the effect on ovulation rate and ovarian steroidogenesis. Unstimulated control ovaries did not ovulate whereas addition of ovine LH (0.1 microgram/ml) and IBMX (0.2mM) resulted in 17.6 +/- 2.7 ovulations per treated ovary. Presence of mifepristone at 1 microM did not significantly inhibit LH+IBMX-induced ovulation (13.0 +/- 1.2) whereas mifepristone at 50 microM significantly (p < 0.01) inhibited ovulation (2.8 +/- 1.4). When the latter dosage of mifepristone (50 microM) was added 4h after LH+IBMX, no inhibitory effect was seen (17.2 +/- 3.0). Progesterone and estradiol release was significantly increased by LH+IBMX over the control group. Presence of mifepristone at any tested dose or time of addition did not significantly change the LH+IBMX-stimulated steroid release. It is concluded that mifepristone inhibits ovulation in the rat at the ovarian level when present just before LH stimulation but not when administered 4h into the ovulatory process.

1-Methyl-3-isobutylxanthine↗
PubMed2004

Matrix metalloproteinase-2 and -9 secretion by the equine ovary during follicular growth and prior to ovulation.

Profound hormonally controlled tissue remodelling occurs in the equine ovary for follicle growth and development, and also for the alteration in follicle shape directed towards the ovulation fossa, the site where ovulation occurs. The aim of this study was to examine the spatial and temporal regulation of matrix metalloproteinases (MMP)-2 and MMP-9, important enzymes in tissue remodelling, during follicle growth, and ovulation. Using gelatin substrate zymography, we measured these MMPs in follicular fluid of large anovulatory follicles collected during spring transition, early dominant follicles (> 23 mm), and at oestrus in follicles approximately 3 days prior to ovulation, and post-hCG treatment when ovulation was predicted in approximately 4 h. The most abundant activity detected in follicular fluid was MMP-2, although there were no changes in secretion or activation in association with ovulation. The activity of MMP-9 was detected in lower amounts, with no changes prior to ovulation, although it decreased significantly (P < 0.05) post-hCG treatment. At oestrus, when different regions of the ovary were maintained in explant culture for 24 h, there were no significant changes in either MMP-2 or MMP-9 secretion by stromal tissues collected at the ovarian fossa, adjacent to the preovulatory follicle but away from the fossa, and a further site remote from the preovulatory follicle. Over this same time period, follicular progesterone (P < 0.01) and oestradiol (P < 0.05) increased significantly, although oestradiol tended to decrease after hCG administration. These findings indicate that MMP-2 and MMP-9 are not key acute regulators for the changes in follicle shape immediately prior to ovulation.

Animals↗
PubMed2004

Suppression of ovulation by a new subcutaneous depot medroxyprogesterone acetate (104 mg/0.65 mL) contraceptive formulation in Asian women.

BACKGROUND: A new progestin-only, nondaily depot medroxyprogesterone acetate (DMPA) SC injectable contraceptive suspension (104 mg/0.65 mL) has been developed. Clinical trials (including dose-ranging, pharmacokinetic/pharmacodynamic, and contraceptive efficacy studies) indicating the effectiveness of this new formulation were conducted primarily in white women. However, results of an early study by the World Health Organization suggested that in Thai women, medroxyprogesterone acetate (MPA) may be metabolized in <91 +/- 7 days (the range for effective suppression of ovulation established in clinical trials), resulting in a faster return to ovulation in this population. OBJECTIVES: This study was designed to determine the duration of ovulation suppression and investigate the pharmacokinetic profile of MPA after a single SC injection of DMPA 104 mg/0.65 mL in Asian women. It also assessed the effect of ethnicity and injection site on the duration of ovulation suppression. METHODS: : This was a single-center, single-dose, open-label outpatient trial conducted in Singapore in Asian women aged 18 to 40 years. After 1 control cycle, women with confirmed ovulation were randomized in a 1:1 ratio to receive an SC injection of DMPA 104 mg/0.65 mL in either the anterior thigh or the abdomen. Serum concentrations of MPA, progesterone, estradiol, luteinizing hormone, and follicle-stimulating hormone were measured during the 91-day dosing interval and for an additional 15 days thereafter. RESULTS: Twenty-four Asian women (mean [SD] age, 33.8 [43] years; range, 22.7-40.1 years; mean [SD] body mass index, 22.4 [3.0] kg/m(2)) belonging to 5 ethnic groups (Chinese, Filipino, Indian, Malaysian, and Thai) were included in the study Ovulation suppression was maintained throughout the 91-day dosing interval, regardless of ethnicity or injection site. Ovulation was suppressed for at least 112 days after injection in 23 (95.8%) women, as evidenced by maintenance of serum progesterone concentrations <4.7 ng/mL. The pharmacokinetic parameters for MPA in these Asian women were similar to those previously reported in white women. The most frequently reported adverse events were flulike symptoms and headache, all of mild to moderate intensity. No serious adverse events were reported. CONCLUSIONS: In this study, SC DMPA 104 mg/0.65 mL provided effective suppression of ovulation for at least 91 days in Asian women. Ethnicity and injection site had no effect on MPA profiles.

Adult↗