Vaginal micronized progesterone on preventing luteinizing hormone untimely surge in ART cycles: A prospective proof-of-concept study.

OBJECTIVE: A new approach to evaluate whether Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone was as effective as using dydrogesterone in suppress LH pulse surge in young women under stimulation in an oocyte donor programme. METHODS: This prospective study included 21 patients aged 19 to 32 years-old stimulated with Elonva® 150, associated or not with Menopur® or Merional® (75 or 150IU) since the beginning of the cycle, plus HMG 150-225IU after the 8th day or just HMG 150-300IU per day. Patients were placed in a PPOS protocol with micronized vaginal progesterone (MVP) 200 mg (Gynpro® Exeltis or Junno Farmoquimica) every 12 hours or dydrogesterone (Duphaston® Abbott) 10 mg every 8 hours from the start of stimulation until the day after the GnRH trigger with Triptorelin 0.2 mg (Gonapeptyl daily®). The primary endpoint was the prevention of untimely LH surge, and secondarily the number of 16 mm follicles, retrieved oocytes and metafase II. RESULTS: Fourteen oocyte donor patients were prescribed MVP while seven others received dydrogesterone (DYG).The gonadotropin protocols included 04 with Corifollitropin alfa 150 plus HMG since the beginning and complemented after the 7th day, and 17 times of just HMG. There was no diferences in the number of follicles >10≤15mm, ≥16mm or number of metafase II oocytes. There was no untimely LH surge on both groups and no OHSS was developed after the agonist trigger. CONCLUSIONS: Progestin-Primed Ovarian Stimulation with micronized vaginal progesterone seems to be a compelling choice for preventing premature ovulation without compromising oocyte quality in women undergoing ovarian stimulation.

Successful pregnancy outcome after fresh embryo transfer in a dual stimulation cycle - a case report.

Controlled ovarian stimulation by antagonist protocol sometimes presents unpleasant surprises in the form of unexpected premature rupture of follicles despite well-timed daily administration of the antagonist. In such cases ovum pick up cannot be done, dual stimulation of the next crop of follicles may be pursued to salvage the cycle. A 'freeze all' strategy is usually implemented in all cases of dual stimulation because of embryo-endometrial asynchrony. Here we present a case where dual stimulation was followed by fresh embryo transfer with a successful pregnancy outcome.

Medroxyprogesterone Acetate versus Gonadotropin-Releasing Hormone Antagonist for the Prevention of Premature Luteinizing Hormone Surge in hyper-responder women undergoing controlled ovarian stimulation for IVF/ICSI Cycles.

OBJECTIVE: To compare the effect of Medroxyprogesterone acetate versus Gonadotropin releasing hormone antagonist for the prevention of premature luteinizing hormone (LH) surge in infertile hyper-responder women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) cycles. METHODS: One hundred infertile hyper-responder women who were candidate for IVF/ICSI were randomly assigned into two groups. Group 1 was given 20 mg Medroxyprogesterone acetate from day 1 of the menstrual cycle till trigger day. Group 2 was given GnRH antagonist (injection Cetrorelix 0.25 mg s/c) from the day when the leading follicle reached 14 mm until the day of trigger for the prevention of premature LH surge (flexible protocol). We measured LH serum levels on day 1, day 7 of cycle and on trigger day. The primary outcome measured was the incidence of premature LH surge. Other outcome measures were total number of mature follicles on trigger day, total number of mature oocytes retrieved and number of good quality day-3 embryos. RESULTS: There was no premature luteinizing hormone surge in both groups of our study. The mean number of follicles on trigger day, mean number of M2 oocytes retrieved and mean number of good quality day-3 embryos were comparable in both the groups, with no statistically significant difference. CONCLUSIONS: The results of this study stated that MPA can be an effective alternative to GnRH antagonist for the prevention of premature LH surge in hyper-responder women undergoing COS for IVF. It is easy to use, widely available and cost-effective. It may establish a new regimen of ovarian stimulation using MPA as an oral alternative to GnRH antagonist treatment in hyper-responders.

Multiple matings modify the estrous length, the moment of ovulation, and the estradiol and LH patterns in ewes.

In several species, mating reduces the estrous length and advances ovulation. The aim of this study was to determine if multiple matings reduces the estrous length and modifies the moment of ovulation, as well as the estradiol and LH patterns in ewes. The estrous cycle of Corriedale ewes was synchronized, and the onset of receptivity was monitored every 3 h with rams, avoiding mating. At the estrous onset, ewes were assigned to two experimental groups (n=10 each): 1) estrous was monitored every 3 h with a ram avoiding mating (group CON), and 2) a ram was allowed to mate and ejaculate once every 3 h (group MAT). The ovaries were scanned with transrectal ultrasonography and blood samples were collected for measuring 17ß-estradiol and LH concentrations every 3 h until ovulation. Estrus was shorter in MAT than CON ewes (24.7 ± 1.5 h vs. 30.4 ± 1.5 h, respectively; P=0.02); the proportion of animals that ovulated before the end of estrus was greater in CON ewes: (9/10 vs. 3/10, P=0.009). The area under the LH curve (AUC) was greater in MAT than CON ewes (36.1 ± 3.5 ng.h-1.mL-1 vs 24.9 ± 3.5 ng.h-1.mL-1 P=0.03). However, MAT ewes had a lower 17ß-estradiol AUC than CON ewes (41.0 ± 4.9 pg.h-1.mL-1 vs 59.4 ± 4.9 pg.h-1.mL-1 P=0.01). Mating reduced the estrous length, induced a greater secretion of LH but less total 17ß-estradiol secreted and, additionally, ovulation occurred more frequently after the end of estrus in mated ewes.

Multiple matings modify the estrous length, the moment of ovulation, and the estradiol and LH patterns in ewes

Abstract In several species, mating reduces the estrous length and advances ovulation. The aim of this study was to determine if multiple matings reduces the estrous length and modifies the moment of ovulation, as well as the estradiol and LH patterns in ewes. The estrous cycle of Corriedale ewes was synchronized, and the onset of receptivity was monitored every 3 h with rams, avoiding mating. At the estrous onset, ewes were assigned to two experimental groups (n=10 each): 1) estrous was monitored every 3 h with a ram avoiding mating (group CON), and 2) a ram was allowed to mate and ejaculate once every 3 h (group MAT). The ovaries were scanned with transrectal ultrasonography and blood samples were collected for measuring 17β-estradiol and LH concentrations every 3 h until ovulation. Estrus was shorter in MAT than CON ewes (24.7 ± 1.5 h vs. 30.4 ± 1.5 h, respectively; P=0.02); the proportion of animals that ovulated before the end of estrus was greater in CON ewes: (9/10 vs. 3/10, P=0.009). The area under the LH curve (AUC) was greater in MAT than CON ewes (36.1 ± 3.5 ng.h-1.mL-1 vs 24.9 ± 3.5 ng.h-1.mL-1 P=0.03). However, MAT ewes had a lower 17β-estradiol AUC than CON ewes (41.0 ± 4.9 pg.h-1.mL-1 vs 59.4 ± 4.9 pg.h-1.mL-1 P=0.01). Mating reduced the estrous length, induced a greater secretion of LH but less total 17β-estradiol secreted and, additionally, ovulation occurred more frequently after the end of estrus in mated ewes.

Multiple matings modify the estrous length, the moment of ovulation, and the estradiol and LH patterns in ewes

In several species, mating reduces the estrous length and advances ovulation. The aim of this study was to determine if multiple matings reduces the estrous length and modifies the moment of ovulation, as well as the estradiol and LH patterns in ewes. The estrous cycle of Corriedale ewes was synchronized, and the onset of receptivity was monitored every 3 h with rams, avoiding mating. At the estrous onset, ewes were assigned to two experimental groups (n=10 each): 1) estrous was monitored every 3 h with a ram avoiding mating (group CON), and 2) a ram was allowed to mate and ejaculate once every 3 h (group MAT). The ovaries were scanned with transrectal ultrasonography and blood samples were collected for measuring 17β-estradiol and LH concentrations every 3 h until ovulation. Estrus was shorter in MAT than CON ewes (24.7 ± 1.5 h vs. 30.4 ± 1.5 h, respectively; P=0.02); the proportion of animals that ovulated before the end of estrus was greater in CON ewes: (9/10 vs. 3/10, P=0.009). The area under the LH curve (AUC) was greater in MAT than CON ewes (36.1 ± 3.5 ng.h-1.mL-1 vs 24.9 ± 3.5 ng.h-1.mL-1 P=0.03). However, MAT ewes had a lower 17β-estradiol AUC than CON ewes (41.0 ± 4.9 pg.h-1.mL-1 vs 59.4 ± 4.9 pg.h-1.mL-1 P=0.01). Mating reduced the estrous length, induced a greater secretion of LH but less total 17β-estradiol secreted and, additionally, ovulation occurred more frequently after the end of estrus in mated ewes.(AU)

Ulipristal acetate prevents ovulation more effectively than levonorgestrel: analysis of pooled data from three randomized trials of emergency contraception regimens.

BACKGROUND: The days just prior to ovulation are the most crucial for emergency contraception (EC) efficacy. Ulipristal acetate (UPA) and levonorgestrel's (LNG) capacity to inhibit follicular rupture have never been compared directly at this time of the cycle. STUDY DESIGN: Raw data from three pharmacodynamics studies with similar methodology were pooled to allow direct comparison of UPA, LNG and LNG + meloxicam's ability to prevent ovulation when administered orally in the advanced follicular phase, with a leading follicle of ≥ 18 mm. RESULTS: Forty eight LNG-treated (1.5 mg) cycles, 31 LNG (1.5 mg) + meloxicam (15 mg), 34 UPA (30 mg) cycles and 50 placebo cycles were compared. Follicle rupture was delayed for at least 5 days in 14.6%, 38.7%, 58.8% and 4% of the LNG-, LNG + meloxicam-, UPA- and placebo-treated cycles, respectively. UPA was more effective than LNG and placebo in inhibiting follicular rupture (p = .0001), while LNG, when administered at this time of the cycle, was not different than placebo. The addition of meloxicam improved the efficacy of LNG in preventing follicular rupture (p = .0292 vs. LNG; p = .0001 vs. placebo; non-significant vs. UPA). UPA was effective in preventing rupture in the 5 days following treatment, even when administered at the time of the luteinizing hormone (LH) surge (UPA 79%, LNG 14% and placebo 10%). None of the treatments were effective when administered on the day of the LH peak. The median time from treatment to rupture was 6 days during the ulipristal cycles and 2 days in the placebo and LNG/LNG + meloxicam cycles (p = .0015). CONCLUSION: Although no EC treatment is 100% effective in inhibiting follicular rupture when administered in the late follicular phase, UPA is the most effective treatment, delaying ovulation for at least 5 days in 59% of the cycles. LNG is not different from placebo in inhibiting follicular rupture at this advanced phase of the cycle. No treatment was effective in postponing rupture when administered on the day of LH peak.

Endocrine control of ovarian function in dogs and other carnivores

Ovarian function in dogs is minimally but successfully evolved and adapted for fertility, and represents a basic model for examining the more complex evolution of ovarian activity in other carnivores and mammals in general. Canids are monoestrous, polytocous, spontaneous ovulators with a spontaneous luteal function producing progesterone for the duration of a normal 2-month pregnancy and unaffected by hysterectomy. They have no acute luteolytic mechanism in the absence of pregnancy although PGF is luteolytic and participates in prepartum luteolysis. The cellular mechanisms of luteal and follicular tissues appear unlikely to differ meaningfully from those described in other species, with the spontaneously prolonged luteal function being similar to, and in some instances shorter than, the luteal lifespan of hysterectomized polyestrous species. All or nearly all female caniform carnivore species have photo-entrained annual life-cycles and annual or biennial reproduction. However, the domestic dog, a subspecies of the grey wolf, is an exception and non-seasonal; but, as an exception to the exception, the basenji dog like the dingo, another wolf subspecies, is seasonal, having its cycle in the autumn. The canine obligate anestrus lasts 2-10 months and is terminated by increased GnRH and LH pulsatility. The timing is under multiple regulatory inputs. These include recovery from progesterone effects at variable times after progesterone declines to nadir values; increased dopaminergic and/or decreased opioidergic tones and/or sensitivities, presumably under the influence of an endogenous circannual cycle assumed to persists despite the lack of photoresponsiveness; and, stimulatory pheromonal input from other females (as well as photoperiod in the case of Basenji). The only clear adaptations or unique attributes seen in dogs that are likely beyond what occurred in a more primitive ancestor are two. One, there is a pregnancy specific increase in prolactin that as a potent luteotrophin (as in rodents) acts to enhance progesterone production during pregnancy, which appears likely to be the case in all carnivores. And, two, the bitch has a fertile-mating window as wide as 11 days, and up to 8 days after ovulation. The latter involves the delayed post-ovulatory maturation of oocytes (also seen in foxes), prolonged post-maturation oocyte viability, and a uterine environment hospitable to sperm survival for up to 7 days during estrus. This relative simplicity contrasts to more complicated adaptive strategies like (1) delayed implantation seen in many caniform carnivores (including many mustelids, ursids, and phocid and otarid seals); (2) reflex, induced ovulation (as seen in many feliform carnivores); and (3) prolongation of post-implantation gestation via placental secretion of progesterone (some feliform, some artiodactyls, primates) or gonadotrophin (primates, equids). Also considered in the review are the endocrine mechanisms triggering the LH surge and estrus behavior in dogs, and factors involved in termination of obligate anestrus.(AU)

Endocrine control of ovarian function in dogs and other carnivores

Ovarian function in dogs is minimally but successfully evolved and adapted for fertility, and represents a basic model for examining the more complex evolution of ovarian activity in other carnivores and mammals in general. Canids are monoestrous, polytocous, spontaneous ovulators with a spontaneous luteal function producing progesterone for the duration of a normal 2-month pregnancy and unaffected by hysterectomy. They have no acute luteolytic mechanism in the absence of pregnancy although PGF is luteolytic and participates in prepartum luteolysis. The cellular mechanisms of luteal and follicular tissues appear unlikely to differ meaningfully from those described in other species, with the spontaneously prolonged luteal function being similar to, and in some instances shorter than, the luteal lifespan of hysterectomized polyestrous species. All or nearly all female caniform carnivore species have photo-entrained annual life-cycles and annual or biennial reproduction. However, the domestic dog, a subspecies of the grey wolf, is an exception and non-seasonal; but, as an exception to the exception, the basenji dog like the dingo, another wolf subspecies, is seasonal, having its cycle in the autumn. The canine obligate anestrus lasts 2-10 months and is terminated by increased GnRH and LH pulsatility. The timing is under multiple regulatory inputs. These include recovery from progesterone effects at variable times after progesterone declines to nadir values; increased dopaminergic and/or decreased opioidergic tones and/or sensitivities, presumably under the influence of an endogenous circannual cycle assumed to persists despite the lack of photoresponsiveness; and, stimulatory pheromonal input from other females (as well as photoperiod in the case of Basenji). The only clear adaptations or unique attributes seen in dogs that are likely beyond what occurred in a more primitive ancestor are two. One, there is a pregnancy specific increase in prolactin that as a potent luteotrophin (as in rodents) acts to enhance progesterone production during pregnancy, which appears likely to be the case in all carnivores. And, two, the bitch has a fertile-mating window as wide as 11 days, and up to 8 days after ovulation. The latter involves the delayed post-ovulatory maturation of oocytes (also seen in foxes), prolonged post-maturation oocyte viability, and a uterine environment hospitable to sperm survival for up to 7 days during estrus. This relative simplicity contrasts to more complicated adaptive strategies like (1) delayed implantation seen in many caniform carnivores (including many mustelids, ursids, and phocid and otarid seals); (2) reflex, induced ovulation (as seen in many feliform carnivores); and (3) prolongation of post-implantation gestation via placental secretion of progesterone (some feliform, some artiodactyls, primates) or gonadotrophin (primates, equids). Also considered in the review are the endocrine mechanisms triggering the LH surge and estrus behavior in dogs, and factors involved in termination of obligate anestrus.