Delay In Ovulation Research Articles

Ibuprofen delays ovulation by several hours: prospective controlled study in natural cycles with HCG-triggered ovulation

Research questionDoes ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DesignTwo-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3 × 400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. ResultsA total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). ConclusionsWomen trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.

Effect of oestrus synchronisation through ovulation delay by vaccination against foot-and-mouth disease in Hanwoo (Bos taurus coreanae) cows.

In Korean cattle, after foot-and-mouth disease (FMD) vaccination, anovulation increases, acute immune response is stimulated. Here, we aimed to improve the fertility rate by ovulation delay caused by the foot-and-mouth disease vaccine. 160 cows (control, FMD, FMD+Gn250 and FMD+Gn500 groups, with 40 cows each) were used. We analysed the ovulation delay, ovulation rate, conception rate and acute-phase immune responses. In the group vaccinated only with FMD, the average follicle size was maintained at 12mm and ovulation was delayed. The ovulation rate of the FMD+Gn500 group (500μg gonadotropin-releasing hormone (GnRH) injections 3 days after the FMD vaccination) was the highest at 81.8%. The ovulation rate of the FMD+Gn250 group (250μg GnRH injections 3 days after FMD vaccination) was 54.5%, and that of the control group (not FMD vaccinated) was 53.3%. The conception rate was 52.5% (19/40) in the control group, 37.5% (15/40) in the FMD+Gn250 group, and 67.5% (27/40) in the FMD+Gn500 group. Analysis of acute-phase immune response revealed that the plasma contents of haptoglobin and serum amyloid A increased up to 7 days after vaccination against FMD in all the experimental groups, except the control group. We concluded that ovulation delay can be employed to improve conception rate after FMD vaccination through a modified ovulation synchronisation method with GnRH.

Granulosa Cell Specific Loss of Adar in Mice Delays Ovulation, Oocyte Maturation and Leads to Infertility.

Adenosine deaminases acting on RNA-(ADAR) comprise one family of RNA editing enzymes that specifically catalyze adenosine to inosine (A-to-I) editing. A granulosa cell (GC) specific Adar depleted mouse model [Adar flox/flox:Cyp19a1-Cre/+ (gcAdarKO)] was used to evaluate the role of ADAR1 during the periovulatory period. Loss of Adar in GCs led to failure to ovulate at 16 h post-hCG, delayed oocyte germinal vesicle breakdown and severe infertility. RNAseq analysis of GC collected from gcAdarKO and littermate control mice at 0 and 4 h post-hCG following a super-ovulatory dose of eCG (48 h), revealed minimal differences after eCG treatment alone (0 h), consistent with normal folliculogenesis observed histologically and uterine estrogenic responses. In contrast, 300 differential expressed genes (DEGs; >1.5-fold change and FDRP < 0.1) were altered at 4 h post-hCG. Ingenuity pathway analysis identified many downstream targets of estrogen and progesterone pathways, while multiple genes involved in inflammatory responses were upregulated in the gcAdarKO GCs. Temporal expression analysis of GCs at 0, 4, 8, and 12 h post-hCG of Ifi44, Ifit1, Ifit3b, and Oas1g and Ovgp1 confirmed upregulation of these inflammatory and interferon genes and downregulation of Ovgp1 a glycoprotein involved in oocyte zona pellucida stability. Thus, loss of ADAR1 in GCs leads to increased expression of inflammatory and interferon response genes which are temporally linked to ovulation failure, alterations in oocyte developmental progression and infertility.

Impacts of seasonality on gene expression in the Chinese horseshoe bat.

Seasonality can cause changes in many environmental factors which potentially affects gene expression. Here, we used a bat species (Rhinolophus sinicus) from eastern China as a model to explore the molecular mechanisms of seasonal effects, in particular during phenological shifts in the spring and autumn. Based on the analysis of 45 RNA‐seq samples, we found strong seasonal effects on gene expression, with a large number of genes identified as either specific or biased to each season. Weighted gene co‐expression network analysis also identified multiple modules significantly associated with each season. These seasonal genes were further enriched into different functional categories. Consistent with effects of phenological shifts on bats, we found that genes related to promoting food intake were highly expressed in both autumn and spring. In addition, immunity genes were also highly expressed in both seasons although this seasonal immune response had tissue specificity in different seasons. In female bats, genes related to the delay of ovulation (e.g., NPPC, natriuretic peptide precursor type C) were highly expressed in October, while genes associated with the promotion of reproduction (e.g., DIO2, iodothyronine deiodinase 2) were biasedly expressed in April. Lastly, we found multiple known core clock genes in both October‐biased and April‐biased expressed genes, which may be involved in regulating the start and end of hibernation, respectively. Overall, together with studies in other land and aquatic animals, our work supports that seasonal gene expression variations may be a general evolutionary response to environmental changes in wild animals.

Effect of exogenous administration of oxytocin on postpartum follicular dynamics, oestrous rate and ovulation in Nili-Ravi buffaloes.

Based on different surveys, dairy farmers are concerned about extensive use of exogenous oxytocin in buffaloes, which is being held responsible for reproductive problems including irregular oestrous cycle and delayed ovulation. For these concerns, effects of oxytocin injection on postpartum follicular dynamics, postpartum oestrous interval (PEI), oestrous length, the interval from onset of estrus to ovulation and blood progesterone (P4) were studied in Nili-Ravi buffaloes. For this purpose, 23 animals within 1week after calving were randomly divided into three groups: without oxytocin (CON; n=7), 10 i.u. oxytocin (LOW; n=8), 30 i.u. oxytocin - (HIGH; n=8) and used to record the PEI for the study period of 154days. At subsequent estrus, three buffaloes from each group (not served) were selected randomly to monitor two cycles for 6weeks. Transrectal ultrasonography was performed to evaluate follicular and corpus luteum (CL) development, and blood sampling was done for progesterone (P4) analysis. These results revealed that postpartum oestrous interval (PEI) decreased significantly in oxytocin-treated groups. The number of small, medium and total follicles on the left ovary was significantly higher in the HIGH group. However, an overall number of small and total follicles on both right and left ovaries was significantly higher in CON and HIGH groups. On the other hand, there was no difference in the number of follicles on the right ovary among all treatment groups. The same was true for the size of pre-ovulatory follicles, CL, P4 concentrations and oestrous cycle length. The intervals from onset of estrus to ovulation and from standing estrus to ovulation were increased considerably in the HIGH group. It is concluded that exogenous oxytocin administration resulted in the shortening of PEI but triggered a delay in ovulation. Moreover, a higher dose of oxytocin could stimulate the growth of small, medium, and total follicles in postpartum Nili-Ravi buffaloes.

Subfertility in Buffaloes and the Association of Detected Milk Microbes

Lactogenesis is a complex physiology and an outcome of a successful reproductive cycle in mammalians. The purpose itself is to nourish the newborn with the nutrients necessary for its protection and growth a continuation from the in utero survival strategy. Thus, mammary development and physiology are intriguingly linked to the uterine changes that happen in a normal reproductive individual. Milk is a highly nutritious food that also favours the growth of microorganisms that can enter through the bloodstream or the discharge system. Briefly, the mastitis-induced release of inflammation mediators such as cytokines, interleukins, and prostaglandin F2α are established to be associated with infertility. Before breeding, mastitis can disrupt hormonal patterns (depression of estradiol production, delayed surge of luteinizing hormone) and delay ovulation. The issue of clinical mastitis is obvious but when subclinical mastitis persists for long the problem gets compounded. Thus, microbes get easily established in the mammary glands of buffaloes whose udder and teat anatomy, love for dirt, and swamp to wallow makes them more vulnerable exposing them to various kinds of pathogenic and opportunistic microbes. Buffaloes, by nature, have issues with silent heat, seasonal anestrus, more sensitive to direct radiation heat stress when faced with a pathological attack of infectious microbes in the milk chamber compromises their fertility.

The potential for intramuscular depot medroxyprogesterone acetate as a self-bridging emergency contraceptive

ObjectiveTo examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development. Study designWe assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14 mm, 15–17 mm and ≥18 mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24 h after DMPA administration to examine against ovulatory outcomes. ResultsTwenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12–14 mm: 0/10 (0%); 15–17 mm: 3/10 (30%); ≥18 mm: 6/6 (100%); p < .01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7 IU/L (mean 49.0 IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression. ConclusionDMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge. ImplicationsDMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.

The use of progestins in equine medicine: A review

SummaryProgesterone is in constant fluctuation throughout the lifespan of the horse. As a key regulator of the hypothalamic–pituitary–gonadal axis, progesterone is involved in numerous aspects of reproduction. Synthetic analogs of progesterone, deemed progestins, are widely available to industry to act as progestogenic within the reproductive tract, although few are bioactive in the horse. Utilised to suppress oestrous, delay ovulation, maintain pregnancy, and for behavioural modifications, progestins are a commonly administered class of pharmaceuticals in veterinary medicine. In this review, we discuss the progestins available to equine industry, in addition to assessing efficacy, pharmacokinetics, and potential side effects following administration of each.

Impaired oocyte maturation and ovulation in membrane progestin receptor (mPR) knockouts in zebrafish

Accumulating evidence suggest that membrane progestin receptor α (mPRα) is the membrane receptor mediating nongenomic progestin signaling that induces oocyte maturation in teleost. However, the involvement of other members of mPR family in oocyte maturation is still unclear. In this study, we found impaired oocyte maturation in zebrafish lacking mPRα1, mPRα2, mPRβ, or mPRγ2. In contrast, no difference was observed in oocyte maturation in the single knockout of mPRγ1, mPRδ, or mPRε. To study possible redundant functions of different mPRs in oocyte maturation, we generated a zebrafish line lacking all seven kinds of mPRs (mprs−/−). We found oocyte maturation was further impaired in mprs−/−. In addition, oocyte ovulation delay was observed in mprs−/− females, which was associated with low levels of nuclear progestin receptor (Pgr), a key regulator for ovulation. We also found reduced fertility in mprs−/− female zebrafish. Furthermore, eggs spawned by mprs−/− females were of poor quality.

Intrafollicular lipopolysaccharide injection delays ovulation in cows

The aim of this study was to evaluate effects of intra-follicular (i.f.) treatment with lipopolysaccharide (LPS) on follicular and luteal development in cows. There were 18 non-lactating cows assigned to two groups to address this aim: control group (n = 9), which received an i.f. injection of saline; and LPS group (n = 9), which received an i.f. injection of 1 μg of LPS per mL of follicular fluid. Cows were treated with an intravaginal P4 releasing device (IVD) and estradiol benzoate on D0. On D4 and D5 cows were treated with cloprostenol sodium and on D7 the IVD was removed. At 12 h after IVD removal, cows were administered the i.f. injection of LPS or saline. After administration of these treatments, follicular development was evaluated every 12 h until ovulation. The LPS treatment increased blood flow in pre-ovulatory follicles (P = 0.05). Follicle growth was reduced by LPS injection (P < 0.02) resulting a longer period to the time of ovulation for cows in the LPS than control group (P = 0.03). The percentage of cows having ovulations was less for the LPS than control group (P = 0.03). The diameter of the CL, CL blood flow and P4 concentrations 5 and 12 days after ovulation did not differ between groups (P> 0.05). In conclusion, intra-follicular treatment with LPS resulted in a decreased rate of follicle growth, delayed timing of ovulations and a lesser number of cows having ovulations.

Laying interruptions in Yellow Warblers (Setophaga petechia)

ABSTRACT Laying interruptions, or even a several-day hiatus during egg laying, have been documented in response to a variety of environmental and internal factors. These interruptions alter the laying schedule of the affected female and have been documented to impact final clutch size in some, but not all, species. The Yellow Warbler (Setophaga petechia), a migratory songbird species, is a determinate layer that typically lays one egg every 24 h until clutches are complete—usually 4 or 5 eggs at Delta Marsh, Manitoba. Nesting observations were recorded from 1974 to 2010 at 961 nests in which laying was occasionally interrupted. Laying interruptions influenced the final clutch size in one of 2 ways. (1) Complete clutches were still laid after a possible delay in ovulation past the ‘optimal period.' Five-egg clutches in nests that experienced a laying interruption provide support for this scenario because 5 eggs is accepted as the largest clutch size generally recorded in this population. (2) Warblers inter...

A protocol for ovulation delay in women who cannot use estrogen, including Jewish women with Niddah issues and a pilot study

Orthodox Jewish women abstain from sexual intercourse from the commencement of menstruation until seven days after the end of menstrual bleeding at which point they can immerse themselves in a ritual bath and recommence relations. For women who ovulate prior to commencing intercourse this results in religious infertility. The traditional treatment for religious infertility is oral estrogens in the early follicular phase to delay ovulation. However, certain groups of women have contraindications to oral estrogens. In this group, no treatment options have existed until now. In this study we proposed a treatment protocol substituting the use of gonadotropin releasing hormone-antagonists in the early follicular phase for the oral estrogens. In a small pilot study, we demonstrate that these two protocols have similar outcomes in terms of ovulation delay (p = 1.0) and likelihood of ongoing pregnancy (p = 1.0). This protocol for ovulation delay also has applications in non-Jewish women who need to delay ovulation due to life constraints.

Toxicology of octamethylcyclotetrasiloxane (D4)

Octamethylcyclotetrasiloxane (D4) is a volatile cyclic siloxane used primarily as a monomer or intermediate in the production of some silicon-based polymers widely used in industrial and consumer applications and may be present as a residual impurity in a variety of consumer products. A robust toxicological data set exists for D4. Treatment-related results from a chronic inhalation study conducted in rats are limited to mild effects on the respiratory tract, increases in liver weight, increases in the incidence of uterine endometrial epithelial hyperplasia, and a dose-related trend in the incidence of endometrial adenomas. The observed increases in liver weight appear to be related to the induction of hepatic metabolizing enzymes, similar to those that are induced in the presence of phenobarbital. D4 is not mutagenic or genotoxic in standard in vitro and in vivo tests; therefore, the benign uterine tumors observed likely occur by a non-genotoxic mechanism. Results from mechanistic studies suggest that D4 has very weak estrogenic and antiestrogenic activity, as well as dopamine agonist-like activity. In rats, D4 exposure delays ovulation and hypothesized to prolong exposure of the uterine endometrium to endogenous estrogen. Though this mode of action may play a role in the development of benign uterine tumors in the rat, it is considered unlikely to occur in the human due to the marked differences in cycle regulatory mechanisms. Reproductive effects were observed following D4 exposure in female rats. These effects appear to be related to a delay of the luteinizing hormone (LH) surge, which fails to induce complete ovulation in the rat. However, based on differences in ovulatory control in rats and humans, it appears these effects may be species-specific with no risk or relevance to human health. Results from pharmacokinetic studies indicate that dermal absorption of D4 is limited, due to its high volatility and, if absorbed via dermal, oral or inhalation exposure, the majority of D4 is rapidly cleared from the body, indicating bioaccumulation is unlikely.

Biological relevance of effects following chronic administration of octamethylcyclotetrasiloxane (D4) in Fischer 344 rats

Octamethylcyclotetrasiloxane (D4) is a cyclic siloxane primarily used as a monomer or intermediate in the production of silicone polymers resulting in potential exposure of workers, and potential low level inhalation or dermal exposure for consumers and the general public. Following a two-year inhalation toxicity study with D4 in rats, increases in uterine endometrial cystic hyperplasia and adenomas were observed at the highest concentration of D4 administered (700ppm). No other neoplasms were increased with D4 treatment. In addition, chronic inhalation exposure of rats to D4 induced changes in relative liver and kidney weights, and produced a chronic nephropathy.This manuscript examines the biological relevance and possible modes of action for the effects observed in the F344 rat following chronic inhalation exposure to D4. D4 is not genotoxic and appears to exert its effects through a nongenotoxic mode of action. An alteration in the estrous cycle in the aging F344 rat was the most likely mode of action for the observed uterine effects following chronic inhalation exposure. Data support the conclusion that D4 acts indirectly via a dopamine-like mechanism leading to alteration of the pituitary control of the estrous cycle in aging F344 rats with a decrease in progesterone and an increase in the estrogen/progesterone ratio most likely induced by a decrease in prolactin concentration. D4 also inhibited the pre-ovulatory LH surge causing a delay in ovulation, persistent follicles and thus a prolonged exposure to elevated estrogen in the adult Sprague Dawely rat. A lengthening of the estrous cycle in the F344 rat with an increase in endogenous estrogen was also induced by D4 inhalation. Although the mode of action responsible for induction of uterine adenomas in the female F344 rat has not been clearly confirmed, the subtlety of effects on the effects of D4 on cyclicity may prevent further assessment and definition of the mode of action. The occurrence of uterine endometrial adenoma in the rat is not relevant for human risk characterization because (1) there are differences in ovulatory cycle regulation in rats compared to humans, (2) cystic hyperplasia without atypia in women is not a cancer precursor, and (3) there is no endometrial lesion in women that is directly analogous to endometrial adenoma in the rat. The effects of D4 on liver are due to a phenobarbital-like mechanism that results in induction of cytochrome P450 and other enzymes of xenobiotic biotransformation. The liver effects are adaptive and not adverse. Kidney findings included chonic progressive nephropathy, a rat lesion that has no counterpart in the human and that should not be used in human risk assessment.

СOMPLICATIONS OF PREGNANCY IN WOMEN WITH DIABETES MELLITUS AND POSSIBILITIES OF THEIR CORRECTION

Reproductive disorders in women with pre-gestational diabetes mellitus lead not only to poorer fertility, but to complicated course and poor outcomes of pregnancy for mother and fetus. Compared to general population, patients with pre-gestational diabetes mellitus have higher frequencies of ovulation delay, ovarian dysfunction and infertility, and if they become diabetic before their puberty, they have later menarche and earlier menopause. All this is caused by functional disorders of hypothalamic-hypophyseal-adrenal axis and ovarian insufficiency with significant decrease in progesterone levels. Pre-conceptional existence of diabetes mellitus is associated with high probability of menstrual cycle disorders, infertility, and in case of pregnancy – with its complicated course (congenital malformations, miscarriage, fetoplacental insufficiency, pre-eclampsia). The risk of these abnormalities is increased in case of late diabetic complications and poor glucose control. Babies born to diabetic mothers, beyond fetopathy and fetoplacental insufficiency, suffer from long term central nervous system disorders that may lead to problems in social adaptation. There are no effective treatments for advanced clinical pre-eclampsia and uncontrolled fetoplacental insufficiency that necessitates the pregnancy to be terminated in the interests of mother or fetus. Due to this, in women with pre-gestational diabetes it is reasonable to implement preventive measures including those aimed at the main components of pathophysiology of a number of obstetric complications. In particular, to correct potential complications of pregnancy in women with diabetes mellitus, administration of active forms of folinic acid and normalization of eicosanoid balance with oral polyunsaturated ω-3 fatty acids is indicated during pregnancy planning and during gestation.

Effects of prepartum oilseed supplements on subclinical endometritis, pro- and anti-inflammatory cytokine transcripts in endometrial cells and postpartum ovarian function in dairy cows.

Postpartum uterine infections affect ovarian function and delay ovulation in cattle. As dietary fats can affect immune cell function, we investigated the influence of prepartum diets on postpartum uterine inflammatory status (UIS) as assessed 25±1 days postpartum by endometrial cytology (normal: ≤8% polymorphonuclear cells (PMN) vs subclinical endometritis (SCE): >8% PMN) and associations between SCE, pro- and anti-inflammatory cytokine gene expression and ovarian function. During the last 5 weeks of gestation, dairy cows received a diet supplemented with 8% rolled sunflower (n=10) or canola seed (n=9) or no oilseed (n=9). Ovaries were scanned until 35 days postpartum. Prepartum diets did not influence SCE, but a preovulatory-size follicle developed sooner (P≤0.05), the interval to first ovulation was shorter and the proportion of cows ovulating within 35 days postpartum was greater in the sunflower seed group. Although mRNA expression of cytokines was not affected by diet, cows with SCE had higher (P≤0.05) expression of interleukin-1β (IL1B), interleukin-8 (CXCL8), IL10 and tumour necrosis factor-α (TNF) than normal cows. The interval (mean ± s.e.m.) from calving to preovulatory-size follicle was shorter (P≤0.05) in normal (13.2±0.9 days) than SCE cows (18.7±1.4 days). In summary, a prepartum diet supplemented with sunflower seed positively influenced postpartum ovarian function without affecting UIS or pro- and anti-inflammatory cytokine gene expression in endometrial cells.

A prospective, randomized, pharmacodynamic study of quick-starting a desogestrel progestin-only pill following ulipristal acetate for emergency contraception.

Is there a pharmacodynamic interaction between ulipristal acetate (UPA) 30 mg for emergency contraception and a daily progestin-only contraceptive pill, desogestrel (DSG) 0.75 mg, when initiated the next day? In this study, DSG impaired the ability of UPA to delay ovulation, but UPA had little impact on the onset of contraceptive effects due to DSG. UPA is a progesterone receptor modulator used for emergency contraceptive (EC) at the dose of 30 mg. UPA delays ovulation by at least 5 days when administered in the mid to late follicular phase. In theory, potent progestins could reactivate progesterone signaling that leads to follicle rupture, thereby impacting the effectiveness of UPA as EC. In addition, UPA could alter the onset of the contraceptive effect of progestin-containing contraceptives started immediately after UPA. A single-blind (for observer), placebo-controlled, partial crossover study was conducted in two sites [Dominican Republic (DR) and the Netherlands (NDL)] over 11 months from October 2012 to September 2013. Healthy female volunteers participated in two of the three treatment cycles separated by a washout cycle. Treatment combinations studied were as follows: (i) a single 30 mg dose of UPA followed by 75 µg per day DSG for 20 days, (ii) a single 30 mg dose of UPA followed by 20 days of placebo matching that of DSG (PLB2) or (iii) one tablet of placebo-matching UPA (PLB1) followed by 75 µg per day DSG for 20 days. Participants were randomized to one of the three treatment sequences (UPA + DSG/UPA + PLB2, PLB1 + DSG/UPA + DSG and UPA + PLB2/PLB1 + DSG) when a lead follicle was ≥ 14 to <16 mm diameter on transvaginal ultrasound imaging (TVU). A total of 71 women were included, and 49 were randomized to a first treatment combination of the three period sequences (20 in the DR and 29 in the NDL); 41 of the 49 continued and completed two treatment combinations (20 in the DR and 21 in the NDL). Initiating DSG treatment the day after UPA significantly reduced the ovulation delaying effect of UPA (P = 0.0054). While ovulation occurred in only one of the 29 UPA-only cycles (3%) in the first 5 days, it occurred in 13 of the 29 (45%) UPA + DSG cycles. This was a small, descriptive, pharmacodynamic study in which some findings differed by study site. Distinguishing between a cystic corpus luteum and a luteinized unruptured follicle (LUF) by TVU was difficult in some cases; however, the investigators reached consensus, when the study was still blinded, regarding ovulation based on hormone levels and careful review of daily TVU images. Initiating the use of a DSG progestin-only pill (POP) immediately after UPA reduces the ability of UPA to delay ovulation and thus may decrease its efficacy as EC. If starting a DSG POP after using UPA for EC, and possibly any progestin-only method, consideration should be given to delaying for at least 5 days after UPA intake in order to preserve the ovulation delaying effects of UPA.

Ulipristal Acetate: Critical Review About Endometrial and Ovulatory Effects in Emergency Contraception

The effectiveness of emergency contraception (EC) is usually estimated by comparing the number of observed pregnancies to that of expected pregnancies after unprotected intercourse. Second-generation selective progesterone receptors modulators have been developed and evaluated for EC use. Among these compounds, ulipristal acetate (UPA) has been proven to share the same antiprogestin activity as mifepristone, and as with mifepristone, UPA has been demonstrated to be effective up to 120 hours after unprotected intercourse. The UPA is more effective than levonorgestrel (LNG) in preventing the appearance of clinically evident pregnancies. The LNG delays ovulation only when taken at the beginning of the fertile period; taken later, it is ineffective on ovulation, while it has been proven to impair the subsequent luteal function. The effectiveness of LNG decreases as time elapses and is limited to 72 hours after unprotected intercourse. The UPA maintains consistent effectiveness for 5 days after unprotected intercourse, and this effectiveness is independent on which of these 5 days it is taken. The ability of UPA to delay ovulation decreases progressively as ovulation approaches and is null at the time of the luteinizing hormone (LH) peak: 1 to 2 days before ovulation, UPA behaves as a placebo. The persistent effectiveness of the drug cannot be due to antiovulatory action, as it decreases sharply as LH approaches its peak level. The effectiveness is most likely due to the dramatic endometrial effects of the drug that are produced regardless of when it is taken. These effects are consistently present, as the threshold for altering endometrial morphology is lower than the threshold for altering folliculogenesis.

Delay of Ovulation Due to Diets Containing Levonorgestrel in Cynomolgus Monkeys (&lt;i&gt;Macaca fascicularis&lt;/i&gt;)

This study was undertaken to develop a simple and practical method to control the time of ovulation in cynomolgus monkeys. Diets containing a synthetic gestagen, levonorgestrel (LNG) were given daily to normally cycling female monkeys for 2 weeks, and plasma concentrations of estradiol-17β and progesterone were determined by EIA in order to estimate the time of ovulation. Doses of LNG (0, 3.2, 8, 20, 50, or 125 μg) were given from Day 2 (Day 0 =the first day of menstruation) through Day 15. The numbers of days from the last administration of LNG to the estimated ovulation in the groups treated with LNG at 20 μg and above were significantly greater than those in the controls, and the values in the group treated with LNG at 50 μg were within a narrow range. In a second experiment, LNG was administered at 50 μg in different phases of the menstrual cycle (Days 9-22, 16-29, and 23-36), and the results indicated that ovulation occurred more than 12 days after the last administration in all monkeys, and the number of days from the last administration of LNG to the estimated ovulation in the group treated on Days 16-29 (luteal phase) was significantly greater than that in the group treated on Days 23-36. These results indicate that daily provision of a diet containing 50 μg LNG could be applicable for delaying ovulation, and suggest that the total level of (exogenous and endogenous) progestins is critical for determining the length of ovulation delay in cynomolgus monkeys.

Ulipristal acetate: a new emergency contraceptive

Ulipristal acetate (UPA) is a newly developed emergency contraceptive currently available in the USA and Europe. It is approved as a 30 mg one-time dose taken within 120 h (5 days) of unprotected intercourse or failed contraception. This selective progesterone receptor modulator appears to be more effective than the levonorgestrel-containing emergency contraceptive, which must be taken within 72 h of unprotected intercourse. According to pharmacodynamic trials, UPA delays follicular maturation and ovulation. In addition, UPA may modulate the endometrium. Both Phase III clinical trials found that UPA does not lose efficacy within the 120-h dosing interval. Throughout all phases of clinical studies, UPA was shown to be well tolerated with only minimal adverse drug reactions, all of which are similar to competitor therapies.