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Contralateral ovulation shortens follicular phase length and favours pre-embryo development during ovarian stimulation with clomiphene citrate.

The present study was undertaken to evaluate whether the site of ovulation affects the following follicular phase length and pre-embryo development during infertility treatment with ovarian stimulation using clomiphene citrate. A total of 363 cycles in 97 patients undergoing infertility treatment (182 intrauterine insemination (IUI) cycles in 60 patients and 181 in-vitro fertilization (IVF) cycles in 52 patients) were studied. The cycles were divided into two main groups: preceding unilateral ovulation (PUO) and preceding bilateral ovulation (PBO). In the PUO group, the cycles were subdivided into contralateral ovulation, bilateral ovulation and ipsilateral ovulation. In IVF cycles alone, bilateral ovulations were further divided into bilateral ovulation-contralateral side and bilateral ovulation, ipsilateral side. Contralateral ovulations were seen in 134 of 240 cycles (56%), excluding bilateral ovulation and PBO. The follicular phase length in contralateral ovulation (16.2 +/- 2.6 days, mean +/- SD) was significantly (P < 0.05) shorter than that of ipsilateral ovulation (16.9 +/- 2.8). There were no significant differences of follicular phase length among contralateral ovulation, bilateral ovulation and PBO. Of IVF cycles including contralateral ovulation-ipsilateral ovulation and bilateral ovulation a total of 107 preovulatory follicles was assessed in the contralateral side (contralateral ovulation + bilateral ovulation-contralateral side) and 97 in the ipsilateral side (ipsilateral ovulation + bilateral ovulation, ipsilateral side). The oocyte retrieval rate (88%), fertilization rate (84%), cleavage rate (95%), embryo transfer rate (70%) of contralateral follicles were higher than those of ipsilateral follicles (71, 62, 86, 38% respectively) and those of PBO (76, 62, 87, 41% respectively). The total pregnancy rate of both IUI and IVF did not differ among contralateral ovulation (15%), ipsilateral ovulation (8%), bilateral ovulation (11%) and PBO (10%). The results confirm and extend our previous findings in natural cycles, suggesting that local ovarian factors, e.g. from corpus luteum, affect the health of preovulatory follicle and the enclosed oocyte in the same ovary (ipsilateral) negatively. Contralateral selection of preovulatory follicles in the succeeding cycle shortens the follicular phase length and favours pre-embryo development. The chance of conceiving during ovarian stimulation with clomiphene citrate may thus be affected by the site of ovulation in the previous cycle.

Adult↗

Spontaneous multiple ovulation in the mare and its effect on the incidence of twin embryo collections.

Records from 183 nonlactating mares that experienced spontaneous multiple ovulation were examined to determine if: 1) double ovulations are as likely to be unilateral as bilateral; 2) the interval between two ovulations is shorter when the ovulations are unilateral than when they are bilateral; 3) the mean diameter of the two follicles on the day prior to ovulation is less when the ovulations are synchronous and unilateral; 4) for both unilateral and bilateral ovulation, twin embryos are more likely to be detected when double ovulations are asynchronous; and 5) for both synchronous and asynchronous ovulations, twin embryos are more likely to be detected when the ovulations are bilateral. Mares were teased daily with a stallion and follicular development was assessed daily during estrus by ultrasonography. Mares were inseminated daily during estrus and embryo recovery attempts were performed 6 to 7 d post ovulation. Double ovulations occurred as frequently from the same, as from opposite ovaries. The interval between the double ovulations was not shorter (P > 0.05) in unilateral versus bilateral ovulations. In addition, size of the largest and second largest preovulatory follicles was not altered (P > 0.05) by type of ovulation (bilateral vs unilateral) or synchrony of ovulation. Synchrony of ovulations had no affect (P > 0.05) on the incidence of twin embryos recovered. However, more (P < 0.05) twin embryos were recovered from bilateral ovulators compared to unilateral ovulators.

Journal Article↗

Timing of multiple ovulations in the ewe after treatment with FSH or PMSG with and without GnRH.

Ovulation rate, median time to first ovulation, median time of all ovulations and median time from first to last ovulation were studied by repeated laparoscopy in Merino ewes. Treatments with FSH or PMSG significantly affected ovulation rate (8.4 +/- 0.81 and 7.3 +/- 1.21 respectively, P less than 0.05) and in median time of all ovulations (60 and 54 h respectively after progestagen sponge removal, P less than 0.05). Differences in the median time to first ovulation (60 and 48 h) and median time from first to last ovulation (6 and 6 h) for the respective treatments were not significant. The synchrony of ovulation after both treatments was adversely affected by (1) the occurrence of premature ovulations before the onset of superovulation, (2) variability in the time of commencement of superovulation, and (3) variability in the time from first to last ovulation. Administration of GnRH synchronized the timing of ovulation with both gonadotrophin treatments. This synchrony was due to a reduction in the period during which superovulation began and in the interval from first to last ovulation. The median time of all ovulations was significantly less with FSH + GnRH than with PMSG + GnRH (45 and 48 h after progestagen sponge removal, respectively, P less than 0.05). Administration of GnRH at 16, 20 or 24 h after progestagen sponge removal significantly affected all traits examined except ovulation rate. Administration at 20 and 24 h produced an equally good synchrony of ovulation which was better than that obtained at 16 h. We suggest that the use of GnRH in embryo collection programmes appears justified and is likely to improve embryo yields due to improved rates of fertilization.

Animals↗

Relationship between level of milk production and multiple ovulations in lactating dairy cows.

Our objective was to evaluate factors associated with spontaneous multiple ovulations in lactating dairy cows. Ovaries of cows [n = 267; >50 days in milk (DIM)] were evaluated weekly using ultrasound to determine spontaneous (i.e., no hormonal treatment) ovulation rate starting at 50 DIM and continuing until pregnancy diagnosis. Cows were fitted with a transmitter to record standing activity during estrus, and serum progesterone concentration was assessed weekly starting at wk 1 postpartum for all cows. Overall, 76 (28.5%) cows were anovular and 191 (71.5%) were ovular by 71 DIM. Incidence of anovulation was not associated with level of milk production but was associated with lower body condition. For anovular cows (n = 41) that spontaneously recovered, the multiple ovulation rate at first ovulation was 46.3%. For second and subsequent ovulations (n = 463), the level of milk production for 14 d preceding estrus was associated with increased ovulation rate. To illustrate, incidence of multiple ovulations was 1.6% (2/128), 16.9% (32/189), and 47.9% (70/146) for ovulations when cows were producing <35, 35 to <45, and >or=45 kg/d, respectively. Among cows for which estrous behavior was recorded, those with multiple ovulations (n = 48) had shorter duration of estrus (4.3 +/- 0.7 vs. 9.9 +/- 0.5 h) and higher production (47.2 +/- 0.9 vs. 38.1 +/- 0.5 kg/d) than cows with single ovulations (n = 237). Circulating concentrations of estradiol were lower (5.5 +/- 0.3; n = 15 vs. 7.8 +/- 0.4 pg/mL; n = 71) during periods of estrus with multiple ovulations despite a greater preovulatory follicular volume (4136 +/- 123 vs. 3085 +/- 110 mm(3)). Similarly, serum progesterone concentration 7 d after estrus was lower for cows with multiple than single ovulations (2.5 +/- 0.3 vs. 3.2 +/- 0.1 ng/mL) despite a greater luteal volume (8291 +/- 516 vs. 6405 +/- 158 mm(3)). In summary, the first spontaneous ovulation in anovular cows and a higher level of milk production for 14 d preceding estrus were associated with increased multiple ovulation rate. Additionally, cows with multiple ovulations had lower estradiol at estrus, a shorter duration of estrus, and lower progesterone at 7 d after estrus than cows with single ovulations.

Animals↗

Persistence of the luteal phase following ovulation during altrenogest treatment in mares.

Two experiments were conducted to test the efficacy of altrenogest treatment in mares. The response to 15-d altrenogest treatment (Experiment 1) was characterized in 20 mares that were given 22 mg daily of altrenogest in oil (n = 10) or in gel (n = 10) from Day 10 to 25 after ovulation. In 17 mares, luteolysis occurred during altrenogest treatment (Day 17.7 +/- 0.5), while 2 mares retained their corpus luteum (CL), and 1 mare had a diestrous ovulation on Day 16, resulting in a prolonged luteal phase. Ten of the 17 mares in which the CL had spontaneously regressed returned to estrus after the end of treatment, and ovulated 5.7 +/- 0.8 d after the end of altrenogest treatment. Two of these 17 mares ovulated 2 and 3 d after the end of altrenogest treatment but ovulation was not accompanied by estrous behavior, and 5 mares ovulated during altrenogest treatment resulting in an interovulatory interval of 22.4 +/- 1.1 d (range: 20 to 25d). Five mares which ovulated during altrenogest treatment and 2 mares which ovulated during silent estrus after the end of altrenogest treatment failed to regress the CL around 14 d post ovulation, and had a prolonged luteal phase. In Experiment 2, the effect of altrenogest administered from luteolysis to ovulation on duration of the subsequent luteal period was analyzed. In 6 mares altrenogest was begun on Day 14 post ovulation and continued until the hCG-induced ovulation. The interval from ovulation during altrenogest treatment to spontaneous luteolysis was 45.6 +/- 2.4 d (range: 40 to 54d) in altrenogest-treated mares and was significantly longer than in 10 untreated control mares (14.5 +/- 0.3 d, range: 13 to 16d). The results suggest that the oil and gel altrenogest preparations are equally effective in modulating estrous behavior and time to estrus and ovulation. Altrenogest treatment started late in diestrus appears to result in a high incidence of ovulation during treatment and when luteolysis and ovulation occur during treatment; the subsequent luteal phase is frequently prolonged due to failure of regression of the CL.

Journal Article↗

Prostaglandin production and ovulation during exposure of amphibian ovarian follicles to gonadotropin or phorbol ester in vitro.

Experiments were carried out at different times of hibernation to ascertain whether prostaglandin is produced by Rana ovarian follicles during gonadotropin- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced in vitro ovulation. Ovarian fragments were cultured in amphibian Ringer in the presence or absence of frog pituitary homogenate (FPH, 0.05 gland/ml) or TPA (1 or 10 microM). After various periods of culture, incidence of ovulation was determined and prostaglandin F2 alpha (PGF2 alpha) accumulated in culture medium was measured by radioimmunoassay. FPH and TPA increased PGF2 alpha levels in medium in a dose-dependent manner. The time course of PGF2 alpha secretion and ovulation by FPH or TPA treatment varied during the hibernation period. In early-hibernation, FPH stimulated neither PGF2 alpha secretion nor ovulation while TPA stimulated PGF2 alpha secretion, although it failed to induce ovulation. In mid-hibernation, FPH and TPA effectively stimulated PGF2 alpha secretion and ovulation, but both events took place several hours later than those observed in late-hibernation. Some fragments obtained in mid-hibernation and most obtained in late-hibernation spontaneously produced PGF2 alpha in vitro without FPH or TPA treatment and in some instances spontaneously ovulated. Furthermore, FPH or TPA increased PGF2 alpha levels further or accelerated the time course of secretion by such fragments. In late-hibernation, PGF2 alpha secretion induced with FPH or TPA increased simultaneously with or later than onset of ovulation. Exogenous cAMP (2.5 mM) or 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7, 100 microM), a PKC inactivator, markedly suppressed FPH- or TPA-stimulated PGF2 alpha secretion and ovulation in mid-hibernation. Indomethacin (IM, 5 micrograms/ml) strongly suppressed TPA- or FPH-stimulated PGF2 alpha production by fragments but its effect on ovulation varied among animals and at different times. IM suppressed ovulation of some ovarian fragments obtained in mid-hibernation, but failed to suppress hormone-induced ovulation in late-hibernation. Cycloheximide (5 micrograms/ml) and actinomycin D (1 microgram/ml) effectively suppressed FPH-stimulated PGF2 alpha production and ovulation, whereas actinomycin D reduced but failed to significantly suppress TPA-induced PGF2 alpha production in mid-hibernation. In general, effects of ovulation inhibitors exhibited strong seasonal variations and were less efficient as the breeding season approached. Taken together, the data suggest that elevated levels of PGF2 alpha are associated with spontaneous and hormone-induced ovulation, and PKC mediates gonadotropin induction of PGF2 alpha but not steroid synthesis in Rana ovaries.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Effects of insemination-ovulation interval on fertilization rates and embryo characteristics in dairy cattle.

The objective of this study was to examine effects of the interval between insemination and ovulation on fertilization and embryo characteristics (quality scored as good, fair, poor and degenerate; morphology; number of cell cycles and accessory sperm number) in dairy cattle. Time of ovulation was assessed by ultrasonography (every 4h). Cows were artificially inseminated once between 36h before ovulation and 12h after ovulation. In total 122 oocytes/embryos were recovered 7d after ovulation. Insemination-ovulation interval (12h-intervals) affected fertilization and the percentages of good embryos. Fertilization rates were higher when AI was performed between 36-24 and 24-12h before ovulation (85% and 82%) compared to AI after ovulation (56%). AI between 24 and 12h before ovulation resulted in higher percentages of good embryos (68%) compared to AI after ovulation (6%). Insemination-ovulation interval had no effect on number of accessory sperm cells and number of cell cycles when corrected for embryo quality. This study showed that the insemination-ovulation interval with a high probability of fertilization is quite long (from 36 to 12h before ovulation). However, the insemination-ovulation interval in which this fertilized oocyte has a high probability of developing into a good embryo is shorter (24-12h before ovulation).

Animals↗

Disappearance of the ovulation stigma in baboons (Papio anubis, Papio cynocephalus) as determined by serial laparoscopies during the luteal phase.

OBJECTIVE: To investigate how long an ovulation stigma remains visible as determined by serial laparoscopies performed during the luteal phase in baboons. SUBJECTS AND SETTING: Sixteen female baboons with a normal pelvis (n = 6) and with endometriosis (n = 10) housed at the Institute of Primate Research, Nairobi, Kenya. INTERVENTIONS: Fifty-six laparoscopies were carried out before ovulation (n = 7) and serially during the luteal phase (n = 49; 3 +/- 1 per baboon): 1 to 2 days (n = 2), 4 to 5 days (n = 15), 8 to 9 days (n = 11), 12 to 13 days (n = 12), and 16 to 17 days (n = 9) after ovulation. MAIN OUTCOME MEASURE: During each laparoscopy the ovaries were screened systematically for the presence and size of an ovulation stigma and/or corpus luteum (CL). RESULTS: When the laparoscopy was done within 5 days after ovulation, a fresh ovulation stigma was observed in all nine baboons with a normal pelvis or minimal endometriosis, but only in four of seven animals with mild to severe disease. If a fresh ovulation stigma had been observed within 5 days after ovulation (n = 13), it gradually became smaller but remained visible 8 to 9 days after ovulation in 91%, at 12 to 13 days after ovulation in 75%, and at 16 to 17 days after ovulation in 50% of the primates. CONCLUSION: If a fresh ovulation stigma was observed in baboons within 5 days after ovulation, it diminished in size but remained visible up to 8, 12, and 16 days after ovulation in 91%, 75%, and 50% of animals, respectively. Therefore, diagnostic laparoscopies for the detection of an ovulation stigma in baboons should be performed in the early luteal phase.

Animals↗

Characteristics of human ovulation in natural cycles correlated with age and achievement of pregnancy.

BACKGROUND: The aim of this study was to evaluate whether characteristics of human ovulation correlate with age and pregnancy potential. METHODS: Two groups of women with regular menstrual cycles were included (i.e. one fertile and one infertile group), which were divided into four age groups (< or =29, 30-34, 35-39, > or = 40 years). Monitoring included observations of follicular phase length, whether ovulations occurred from the left or right ovary, the pattern of ovulations in succeeding natural cycles and, in a subset of women, early follicular phase FSH concentrations. RESULTS: Ovulation moving from one ovary to the other in two consecutive cycles (i.e. contralateral ovulation) was inversely correlated with age, showing a ratio of contralateral ovulation per contra plus ipsilateral ovulations (C/C+I) of 62% in women <29 years, gradually decreasing to 42% in women >40 years. The ratio of right-sided ovulation per right plus left-sided ovulations (R/R+L) was unrelated to age and remained almost constant at a level of approximately 55%. The follicular phase length was inversely correlated with age, being 16.2 +/- 2.9, 15.4 +/- 2.9, 14.8 +/- 2.8 and 13.7 +/- 1.3 days in women < 29, 30-34, 35-39 and >40 years of age respectively. The follicular phase length was similar when comparing ovulations occurring from the right and left ovary, but comparing two successive cycles, the length of the follicular phase of the second cycle, showing contralateral ovulation, was shorter than ipsilateral ovulation with two consecutive ovulations in the same ovary. The pregnancy rate of the four groups decreased with age, being 14, 12, 5 and 3% respectively. The C/C+I ratio correlates with pregnancy rate and follicular phase length, and inversely correlates with basal FSH, whereas R/R+L is unrelated to age and pregnancy rate. CONCLUSIONS: Human ovulation shows characteristics related to age. The interaction between the two ovaries seems to be most pronounced in the younger years, where ovulations jump from one ovary to the other more frequently than later on in life. The C/C+I ratio shows a clear correlation with age and pregnancy rate.

Adult↗

Effects of luteinizing hormone, progesterone, testosterone, estradiol and corticosterone on ovulation and luteinizing hormone release in hens treated with aminoglutethimide.

Aminoglutethimide (AG), an inhibitor of steroidogenesis, was administered s.c. to 5 groups of laying hens at a dose of 200 mg AG/kg body weight 9 h before expected midsequence ovulation. This dose has previously been demonstrated to consistently block ovulation. The injection of AG was followed by s.c. injections of: Group 1, 1.0 mg progesterone; Group 2, 0.1 mg estradiol-17 beta; Group 3, 1.5 mg corticosterone, all at 6 h prior to expected ovulation; Group 4, 1.0 mg testosterone at both 8 h and 5 h before expected ovulation; and Group 5, 25 micrograms of ovine luteinizing hormone (LH) at 8 and 50 micrograms ovine LH at 6 h before expected ovulation. For each group, 4 control hens were injected with AG and the appropriate vehicle. Blood samples were taken at 1- or 2-h intervals from the time of AG injection to the expected time of ovulation. The hens were killed 4 h after expected ovulation and examined for the occurrence of ovulation. In all hens injected with vehicle, ovulation and the preovulatory surges of progesterone, testosterone, estradiol-17 beta and LH were inhibited. The plasma concentration of corticosterone was not reduced following an injection of AG. Four of 6 hens ovulated in response to injection of ovine LH, although neither endogenous LH nor progesterone were released. Thus, LH appears to play a direct role in follicular rupture and extrusion of the ovum. The administration of progesterone induced a significant and prolonged rise in LH, restoring AG-blocked ovulation in all hens treated (n = 6). Injections of testosterone restored LH release in all hens and ovulation in 2 of 7 hens treated. Three of 7 hens ovulated in response to the corticosterone injection. A preovulatory rise in LH was not observed, indicating that corticosterone may exert its ovulation-inducing effect directly on the mature follicle. Estradiol-17 beta did not restore LH release or ovulation in any of the hens treated with AG.

Aminoglutethimide↗