Progesterone-based timed AI protocols for Bos indicus cattle II: Reproductive outcomes of either EB or GnRH-type protocol, using or not GnRH at AI.

The aim of these experiments was to study ovarian dynamics and fertility of Bos indicus beef cattle submitted to 7-d progesterone (P4)-based fixed-time AI (FTAI) protocols using different hormonal treatments. In Exp. 1, 2 yr old Nelore heifers (n = 973) were randomly assigned to one of four treatments: EB-0 (estradiol benzoate, EB on D0 and no GnRH at AI), EB-G (EB on D0 and GnRH at AI), G-0 (GnRH on D0 and no GnRH at AI), or G-G (GnRH on D0 and at AI). On D0, heifers received an intravaginal P4 implant (0.5 g) for 7 d and EB (1.5 mg) or GnRH (16.8 µg). On D7, the P4 implant was withdrawn and heifers received cloprostenol (PGF; 0.5 mg) and estradiol cypionate (EC, 0.5 mg). Heifers in G groups also received PGF and eCG (200 IU) on D6, whereas EB heifers received eCG on D7. At FTAI on D9, only EB-G and G-G groups received GnRH (8.4 µg). In Exp. 2, Nelore cows (n = 804) received the same treatments (EB-0, EB-G, G-0, or G-G) using a 1.0 g P4 implant, 2.0 mg EB, and 300 IU eCG. Effects were considered significant when P ≤ 0.05. After treatment on D0, G had more ovulations than EB in heifers (60.3 [287/476] vs. 12.7% [63/497]) and cows (73.7 [83/112] vs. 24.4% [28/113]). Luteolysis after D0 was greater in EB than G in heifers (39.2 [159/406] vs. 20.0% [77/385]) and cows (25.5 [14/55] vs. 1.6% [1/64]). Heifers in G had larger follicles (mm) than EB on D7 (10.3 ± 0.2 vs. 9.2 ± 0.2) and at AI (11.9 ± 0.2 vs. 11.3 ± 0.2). Cows had larger follicles in G than EB on D7 (11.0 ± 0.3 vs. 9.9 ± 0.3) but not at AI. More estrus was observed in G than EB for heifers (80.3 [382/476] vs. 69.6% [346/497]) and cows (67.6 [270/400] vs. 56.2% [227/404]). There was no interaction between D0 and D9 treatments on pregnancy per AI (P/AI) in heifers (EB-0: 56.7 [139/245], EB-G: 53.6 [135/252], G-0: 52.6 [127/241], and G-G: 57.5% [135/235]). However, cows from EB-G had greater P/AI than EB-0 (69.5 [142/204] vs. 60.2% [120/200]), whereas P/AI for G-0 (62.7% [127/203]) was similar to G-G (60.9% [120/197]). In heifers, there was no interaction of GnRH at AI with estrus, however, cows that did not display estrus had greater P/AI if they received GnRH at AI (GnRH = 59.1 [91/154] vs. No GnRH = 48.2% [78/162]). Thus, protocols initiated with EB or GnRH for Bos indicus heifers and cows had differing ovarian dynamics but similar overall fertility, enabling their use in reproductive management programs. Treatment with GnRH at time of AI increased fertility in some instances in Bos indicus cows but not in heifers.

Fertility drugs and cutaneous melanoma risk: a French prospective cohort study.

Cutaneous melanoma has been suspected to be influenced by female sex hormones. A review of the literature in 2018 indicated that fertility drug (FD) use was associated with increased melanoma risk among parous women only. However, most studies so far were based on a retrospective design and the current evidence is unclear. We sought to prospectively investigate the associations between FD use and melanoma risk in women. E3N is a prospective cohort of 98 995 French women aged 40-65 years at inclusion in 1990. Information on use of FDs, including duration and time of administration, was assessed through self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and melanoma risk factors. Over 1990-2008, about 611 melanoma cases were ascertained among 86 653 women. Compared with never use, ever use of FDs was not associated with melanoma risk overall [hazard ratio (HR) = 1.15; 95% confidence interval (CI) = 0.75-1.74], or among parous women (HR = 1.08; 95% CI = 0.67-1.73). Among ever users of FDs, duration of use and age at first use were not associated with melanoma risk. Associations were similar after adjustment for UV exposure, although FD users were more likely to report tanning bed use than never-users (odds ratio = 1.50; CI = 1.01-2.22) in a subsample with recreational UV exposure data. Our data do not support an association between FD use and melanoma risk, but underlie the importance of taking into consideration potential confounding from sun exposure in future research.

Agronomic and Economic Interactions between Sidedressed Nitrogen and Potassium Fertilizations on Atlantic Potato

Abstract Nitrogen (N) and potassium (K) in potato crop planting synergistically increase tuber yield, but there are no studies on this interaction in sidedressing. In two experiments with 'Atlantic' potato combinations of four N rates (0, 50, 100, and 150 kg ha-1) with four K2O rates (0, 100, 200, and 300 kg ha-1) were applied in sidedressing in a 4×4 factorial scheme with three replications in a completely randomized design. Adjacent commercial fields were sampled to economic comparisons with experimental results. Significant interaction between N and K sidedressing rates with tuber yields increase also was confirmed and classified as Liebig-synergism. Compared to the isolated N and K applications in sidedressing, joint N and K fertilizations, respectively, increases by 11% and 48% marketable tuber yields in the summer-fall experiment, and 12% and 7% in the spring experiment. Joint N and K applications as sidedressing was more profitable than planting fertilization, mainly at higher N and K rates. The response of specific gravity of 'Atlantic' potato tubers to the N and K sidedressing rates was mediated by interactions between edaphoclimatic conditions and inputs of N and K. The combined application of N and K sidedressing rates increased specific gravity in the summer-fall experiment, but had a negative effect in the spring experiment. Therefore, our results provide strong evidence that the fertilization management for potato crop in Brazil can be modified by applying higher amounts of N and K in sidedressing to match nutritional needs of the crop.

Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan.

BACKGROUND: The current study evaluated whether the risk of developing thyroid cancer in Asian women was associated with infertility and the use of fertility drugs. METHODS: The authors conducted a large, retrospective cohort study using Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,356 women aged 20 to 49 years who were diagnosed with infertility from 2000 through 2013 were included in the infertile group, and 53,424 women without a history of infertility were selected as fertile comparisons and were frequency matched by age and year of diagnosis. Both groups were followed up to 2013 to calculate incident thyroid cancer. Poisson regression analysis was used to estimate the incidence rate ratio (IRR). RESULTS: The incidence of thyroid cancer was 1.9-fold greater in the infertile group compared with the comparison group (2.85 vs 1.53 per 10,000 person-years), with an adjusted IRR of 1.80 (95% confidence interval [95% CI], 1.70-1.92) for the infertile group. Higher cancer incidence was demonstrated for the infertile group after 7 years of follow-up, with an adjusted IRR of 4.39 (95% CI, 4.03-4.78) compared with the comparison group. Among infertile women, those who had taken the fertility drug clomiphene were found to have a reduced incidence of thyroid cancer compared with those who were treated without the drug (2.69 vs 3.42 per 10,000 person-years), with an adjusted IRR of 0.86 (95% CI, 0.75-0.99). However, the cancer incidence in infertile women being treated with clomiphene was nearly 6-fold greater than that in fertile women taking the drug. CONCLUSIONS: The results of the current study provide evidence that women with infertility are at an increased risk of developing thyroid cancer.

The Role of Reproductive Technologies in Amphibian Conservation Breeding Programs.

Anthropogenic environmental change has led to unprecedented rates of species extinction, presenting a major threat to global biodiversity. Among vertebrates, amphibians have been most severely impacted, with an estimated 41% of species now threatened with extinction. In response to this biodiversity crisis, a moral and ethical obligation exists to implement proactive interventionist conservation actions to assist species recovery and decelerate declines. Conservation breeding programs have been successfully established for several threatened amphibian species globally, aiming to prevent species' extinction by maintaining genetically representative assurance colonies ex situ while providing individuals for population augmentation, translocation, and reestablishment in situ. Reproductive technologies have enormous potential to enhance the propagation and genetic management of threatened species. In this review, we discuss the role of reproductive technologies in amphibian conservation breeding programs and summarize technological advancements in amphibian hormone therapies, gamete storage, and artificial fertilization.

Transepithelial transport across the blood-testis barrier.

The blood-testis barrier protects developing germ cells by limiting the entry of xenobiotics into the adluminal compartment. There is strong evidence that the male genital tract can serve as a sanctuary site, an area of the body where tumors or viruses are able to survive treatments because most drugs are unable to reach therapeutic concentrations. Recent work has classified the expression and localization of endogenous transporters in the male genital tract as well as the discovery of a transepithelial transport pathway as the molecular mechanism by which nucleoside analogs may be able to circumvent the blood-testis barrier. Designing drug therapies that utilize transepithelial transport pathways may improve drug disposition to this sanctuary site. Strategies that improve disposition into the male genital tract could reduce the rate of testicular relapse, decrease viral load in semen, and improve therapeutic strategies for male fertility.

Utilization of the Bologna criteria: a promise unfulfilled? A review of published and unpublished/ongoing trials.

OBJECTIVE: To study the use of the Bologna criteria (BC) for the definition of poor ovarian responders (POR) in clinical practice and research. DESIGN: Systematic review of published and unpublished/ongoing trials between January 2012 and August 2017 on POR. SETTING: Not applicable. PATIENT(S): Not applicable. INTERVENTION(S): The databases were searched using the relevant medical subject headings including all subheadings. The search was limited to humans and English language. The references of the included studies were cross-searched for possibly missed articles. Only clinical trials providing an evidence level ≥ III were included. Case reports, review, letters, and hypothetical articles were excluded. MAIN OUTCOME MEASURE(S): Extracted studies were divided into two groups: studies in which the BC were used or not. RESULT(S): One hundred nine published clinical studies analyzing a total of 30,540 women and 112 unpublished/ongoing trials were identified. The BC were used to define POR in 56 (51%) of the published and 44 (39%) of the unpublished trials. The use of the BC gradually increased from 29% to 53% from 2012 to 2017. Asian researchers were more likely to use the BC compared with European and North American researchers (65%, 49%, and 23%, respectively). Neither the design of the study nor the impact factor of the publishing journal was correlated with the use of the BC. CONCLUSION(S): There is still reluctance to use the BC for the definition of POR, which makes it difficult to combine data from small studies and reach a meaningful conclusion.

Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome.

OBJECTIVE: To compare time to ovulation, ovulation rates, and side effect profile of traditional and the stair-step protocol for ovulation induction using clomiphene citrate in women with polycystic ovary syndrome (PCOS). METHODS: We performed a retrospective study of women seeking care for infertility with a diagnosis of PCOS at a university-based infertility clinic from July 2012 to July 2014. We included patients who were resistant to the initial starting dose of 50 mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes included ovulation rates, clinical pregnancy rates, and mild and moderate-to-severe side effects based on dose. For the traditional protocol, higher doses of clomiphene were used each subsequent month if no ovulation occurred. For the stair-step protocol, higher doses of clomiphene were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. Our study had 80% power to detect a 20% difference in ovulation. RESULTS: One hundred nine patients were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%) in the stair-step protocol. Age and body mass index were similar between groups. The time to ovulation was decreased in the stair-step protocol group compared with the traditional protocol group (23.1±0.9 days vs 47.5±6.3 days). Ovulation rates were increased in the stair-step group compared with the traditional group at 150 mg (16 [37%] vs 8 [12%], P=.004) and at 200 mg (9 [21%] vs 3 [5%], P=.01). Pregnancy rates were similar between groups once ovulation was achieved (12 [18.1%] vs 7 [16.3%], P=.08). The stair-step protocol had an increased incidence of mild side effects (vasomotor flushes, headaches, gastrointestinal disturbance, mastalgia, changes in mood; 18 [41%] vs 8 [12%]), but there was no difference in the incidence of severe side effects (headaches, visual disturbances). CONCLUSION: For women with PCOS, the stair-step clomiphene protocol is associated with decreased time to ovulation and increased ovulation rates at higher doses when compared with the traditional protocol.

Effects of melatonin implantation on the fertility potentials of Kivircik and Charollais ewes and rams during the non-breeding season.

This study examined the effect of melatonin implantation during the non-breeding season on the reproductive performance of ewes and the testicular dimensions of rams. In seasonally anestrus Kivircik and Charollais ewes and rams were subjected to melatonin. Estrus response was significantly higher in treated than control ewes of both breeds (p<0.001). The pregnancy rate was significantly lower (p<0.001) in the control than in the treated animals. The twinning rate was significantly lower in melatonin implanted Kivircik than Charollais ewes (p<0.05). The testicular dimensions after 42 days of melatonin treatment increased in both breeds. Scrotal length (SL) increased in Kivircik and Charollais rams (p<0.01). The increase in scrotal circumference (SC) was more marked in the Charollais (P<0.01) than in the Kivircik rams. There was a large increase in testicular volume (TV) in both Kivircik (p<0.01) and Charollais (p<0.001) rams. This study shows that melatonin implants can be applied to induce estrus in ewes approximately four months earlier than breeding season. Melatonin implantation in the non-breeding season significantly increased testicular dimensions in Kivircik and Charollais rams thus increasing their reproductive potential.

Progesterone luteal support after ovulation induction and intrauterine insemination: an updated systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of progesterone (P) for luteal phase support after ovulation induction (OI) and intrauterine insemination (IUI). DESIGN: An updated systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Patients undergoing OI-IUI for infertility. INTERVENTION(S): Exogenous P luteal support after OI-IUI. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Eleven trials were identified that met inclusion criteria and constituted 2,842 patients undergoing 4,065 cycles, more than doubling the sample size from the previous meta-analysis. In patients receiving gonadotropins for OI, clinical pregnancy (relative risk [RR] 1.56, 95% confidence interval [CI] 1.21-2.02) and live birth (RR 1.77, 95% CI 1.30-2.42) were more likely in P supplemented patients. These findings persisted in analysis of live birth per IUI cycle (RR 1.59, 95% CI 1.24-2.04). There were no data on live birth in clomiphene citrate or clomiphene plus gonadotropin cycles. There was no benefit on clinical pregnancy with P support for patients who underwent OI with clomiphene (RR 0.85, 95% CI 0.52-1.41) or clomiphene plus gonadotropins (RR 1.26, 95% CI 0.90-1.76). CONCLUSION(S): Progesterone luteal phase support is beneficial to patients undergoing ovulation induction with gonadotropins in IUI cycles. The number needed to treat is 11 patients to have one additional live birth. Progesterone support did not benefit patients undergoing ovulation induction with clomiphene citrate or clomiphene plus gonadotropins.

Association of uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination for unexplained infertility.

OBJECTIVE: To investigate the association of non-cavity-distorting uterine fibroids and pregnancy outcomes after ovarian stimulation-intrauterine insemination (OS-IUI) in couples with unexplained infertility. DESIGN: Secondary analysis from a prospective, randomized, multicenter clinical trial investigating fertility outcomes after OS-IUI. SETTING: Reproductive Medicine Network clinical sites. PATIENT(S): Nine hundred couples with unexplained infertility who participated in the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. INTERVENTION(S): Participants were randomized to one of three arms (clomiphene citrate, letrozole, or gonadotropins), and treatment was continued for up to four cycles or until pregnancy was achieved. MAIN OUTCOMES MEASURE(S): Conception (serum hCG increase), clinical pregnancy (fetal cardiac activity), and live birth rates. RESULT(S): A total of 102/900 participants (11.3%) had at least one documented fibroid and a normal uterine cavity. Women with fibroids were older, more likely to be African American, had a greater uterine volume, lower serum antimüllerian hormone levels, and fewer antral follicles than women without fibroids. In conception cycles, clinical pregnancy rates were significantly lower in participants with fibroids than in those without uterine fibroids. Pregnancy loss before 12 weeks was more likely in African American women with fibroids compared with non-African American women with fibroids. There was no difference in conception and live birth rates in subjects with and without fibroids. CONCLUSION(S): No differences were observed in conception and live birth rates in women with non-cavity-distorting fibroids and those without fibroids. These findings provide reassurance that pregnancy success is not impacted in couples with non-cavity-distorting fibroids undergoing OS-IUI for unexplained infertility. CLINICAL TRIAL REGISTRATION NUMBER: NCT01044862.

Fertility-sparing surgery for patients with low-grade endometrial stromal sarcoma.

PURPOSE: To assess the clinical outcomes and fertility of young women with stage I low-grade endometrial stromal sarcoma (ESS) treated with fertility-sparing surgery. RESULTS: Seventeen patients with stage I low-grade ESS (stage IA, n = 6; stage IB, n = 11) were entered into this study. Adjuvant hormone therapy was administered to 15 (88.2%) patients. At a median follow-up of 39 months (range, 4-106 months), 10 (58.8%) patients developed recurrence. All 10 patients had stage IB disease; among them, the first recurrence limited to the uterus was observed in 6 patients. All 17 patients were alive and disease-free at the time of last contact. After treatment, five of eight (62.5%) patients who attempted pregnancy conceived. No offspring had congenital anomalies. METHODS: Patients with stage I low-grade ESS who underwent fertility-sparing surgery between April 2001 and November 2015 were retrospectively reviewed. CONCLUSIONS: Fertility-sparing surgery may be considered for young patients with stage IA low-grade ESS who wish to preserve their fertility.

Is the type of gonadotropin-releasing hormone suppression protocol for ovarian hyperstimulation associated with ectopic pregnancy in fresh autologous cycles for in vitro fertilization?

OBJECTIVE: To evaluate the association between different ovarian hyperstimulation protocols and ectopic pregnancy (EP) in in vitro fertilization (IVF) cycles in fresh autologous embryo transfer cycles in the United States between 2008 and 2011 as reported to the Society of Assisted Reproductive Technology (SART). DESIGN: Historical cohort study. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): All autologous cycles that resulted in a clinical pregnancy after a fresh, intrauterine embryo transfer and described characteristics of cycles according to protocol were included: luteal GnRH agonist, GnRH agonist flare, or GnRH antagonist. Multivariate logistic regression was conducted to investigate the association between type of protocol and EP. RESULT(S): Among 136,605 clinical pregnancies, 2,645 (1.94%) were EP. Ectopic pregnancy was more frequent with GnRH antagonist (2.4%) cycles than with GnRH agonist flare (2.1%) or luteal GnRH agonist (1.6%) cycles. After adjusting for maternal and treatment characteristics, the GnRH antagonist and the GnRH agonist flare protocols were associated with increased odds of EP (adjusted odds ratio [aOR] 1.52; 95% confidence interval [CI], 1.39-1.65; and aOR 1.25; 95% CI, 1.09-1.44, respectively) compared with luteal GnRH agonist. Analysis of differences in the factors related to EP in luteal GnRH agonist versus GnRH antagonist protocols indicated that diminished ovarian reserve was associated with an increased risk of EP in luteal GnRH agonist but not in GnRH antagonist cycles. CONCLUSION(S): The type of protocol used during ovarian hyperstimulation in fresh autologous cycles was associated with EP. This finding suggests a role for extrapituitary GnRH on the tubal and uterine environment during ovarian hyperstimulation treatment for IVF.

Standard human chorionic gonadotropin versus double trigger for final oocyte maturation results in different granulosa cells gene expressions: a pilot study.

OBJECTIVE: To investigate the messenger RNA (mRNA) expression of reproduction-related genes in granulosa cells (GCs) of patients triggered with hCG compared with patients triggered with GnRH agonist and hCG (double trigger) for final oocyte maturation. DESIGN: Granulosa cells were obtained at the time of oocyte retrieval, and gene expression was analyzed using quantitative real-time polymerase chain reaction. SETTING: Referral center. PATIENT(S): Fifteen women undergoing controlled ovarian hyperstimulation for IVF who received hCG for final follicular maturation and in a subsequent IVF cycle received double trigger. INTERVENTION(S): Granulosa cells collection. MAIN OUTCOME MEASURE(S): The expression of genes related to ovarian hyperstimulation syndrome, gap junction, and epidermal-like growth factor in GCs. RESULT(S): The mRNA expressions of amphiregulin (2.1 vs. 1, arbitrary unit) and epiregulin (2.5 vs. 1, arbitrary unit) were significantly higher in the double trigger group compared with the hCG group. We found no difference in luteinizing hormone receptor and follicle stimulating hormone receptor mRNA expressions between the two groups. Moreover, although the mRNA expression of pigment epithelium-derived factor (1.5 vs. 1, arbitrary unit) was significantly higher in the double trigger group, no between-group differences were observed in the expression of vascular endothelial growth factor and GnRH receptor. The mRNA expression of conexin43 in cumulus cells (0.7 vs. 1, arbitrary unit) was significantly lower in the double trigger group compared with the hCG group. CONCLUSION(S): Our findings suggest that the decreased expression of conexin43 and the increased expression of epiregulin and amphiregulin in the GCs from patients receiving the double trigger may explain the suggested improved oocyte and embryo quality related to the double triggering group.

Effect of Palm Pollen on Sperm Parameters of Infertile Man.

There is a rapidly growing trend in the consumption of herbal remedies in the developing countries. The aim of this study was to determine the effects of orally administered Date Palm Pollen (DPP) on the results of semen analysis in adult infertile men. Forty infertile men participated in our study. They were treated by Pollen powder 120 mg kg(-1) in gelatinous capsules every other day, for two months. Before and at the end of therapy, the semen was collected after masturbation and sperm numbers, motility and morphology were determined. Our findings revealed that consumption of DPP improved the sperm count. The treatment was significantly increased sperm motility, morphology and forward progressive motility. Date palm pollen seems to cure male infertility by improving the quality of sperm parameters.

Coenzyme Q10, α-tocopherol, and oxidative stress could be important metabolic biomarkers of male infertility.

Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10, CoQ(10-TOTAL), γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ(10-TOTAL) (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ(10-TOTAL), and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

Factors affecting the success of resynchronization protocols with or without progesterone supplementation in dairy cows.

The objective of this study was to investigate factors that influence the success of resynchronization protocols for bovines with and without progesterone supplementation. Cow synchronized and not found pregnant were randomly assigned to two resynchronization protocols: ovsynch without progesterone (P4) supplementation (n = 66) or with exogenous P4 administered from Days 0 to 7 (n = 67). Progesterone levels were measured on Days 0 and 7 of these protocols as well as 4 and 5 days post-insemination. Progesterone supplementation raised the P4 levels on Day 7 (p < 0.05), but had no overall effect on resynchronization rates (RRs) or pregnancy per artificial insemination (P/AI). However, cows with Body Condition Score (BCS) > 3.5 had increased P/AI values while cows with BCS < 2.75 had decreased P/AI rates after P4 supplementation. Primiparous cows had higher P4 values on Day 7 than pluriparous animals (p = 0.04) and tended to have higher RRs (p = 0.06). Results of this study indicate that progesterone supplementation in resynchronization protocols has minimal effects on outcomes. Parity had an effect on the levels of circulating progesterone at initiation of the protocol, which in turn influenced the RR.

Effects of senktide, a neurokinin 3 receptor agonist, on luteinizing hormone secretion and follicular development in anestrous Shiba goats: a pilot study.

BACKGROUND: Recent studies suggest that neurokinin B and its receptor, neurokinin 3 receptor, have an essential role in the regulation of gonadotropin-releasing hormone and luteinizing hormone (LH) release in several mammalian species. As the first trial, this pilot study reports the effect of intravenous treatment with senktide, a selective agonist of neurokinin 3 receptor, on LH secretion, follicular development in female goats that were clinically diagnosed with anestrus. FINDINGS: Anestrous goats were intravenously administered 200 nmol senktide at 4-h intervals for 24 h. Most of them examined (5/6 cases) showed a pulsatile increase in LH secretion after each injection of senktide, whereas the remaining one case showed a surge-like increase of LH secretion. Ovulation was confirmed in 5/6 cases at the range of 48-96 h after the beginning of treatment. CONCLUSIONS: This pilot study demonstrated that intravenous treatment with senktide has therapeutic action in goats with anestrus by inducing LH release, which could promote follicular development and ovulation.

Effect of interval from induction of puberty to initiation of a timed AI protocol on pregnancy rate in Nellore heifers.

Prepubertal Bos indicus heifers (n = 774) were submitted to an E2/P4-based timed artificial insemination (TAI) protocol at three different intervals after induction of their pubertal ovulation by insertion of an intravaginal progesterone (P4) device for 12 days. Heifers were randomly assigned to start the TAI protocol at 10 (group 10; n = 253), 12 (group 12; n = 265), or 14 (group 14; n = 256) days after the P4 device was removed. The TAI protocol consisted of the following: insertion of intravaginal device containing P4 (Controlled internal drug release [CIDR]; previously used twice for 9 days each) + estradiol benzoate (2 mg) on Day 0, CIDR withdrawal + estradiol cypionate (0.5 mg) and PGF2α (12.5 mg) on Day 9, and TAI on Day 11. A subgroup of heifers (n = 472) was evaluated by ultrasound on Days 9 and 11 to evaluate the ovaries and to determine P4 concentrations on Day 9. On Day 9, more (P < 0.05) CLs were present, and follicular diameter was smaller (P < 0.05) for group 10 than for groups 12 and 14 (38.4%, 29.3%, and 23.3% with CL and 9.4 ± 0.1, 9.9 ± 0.1, and 9.8 ± 0.1 mm diameter, respectively), but P4 concentrations did not differ (P > 0.1) between treatments (2.4 ± 0.06 ng/mL). Follicular diameter at TAI (11.08 ± 0.09 mm) and ovulation rate (88.4%) did not differ between treatments (P > 0.1). However, conception and pregnancy rates for all heifers were greater (P < 0.05) in group 12 (50.4% and 45.5%, respectively) than in group 10 (38.2% and 33.7%, respectively), with group 14 intermediate to other treatments (45.6% and 40.6%, respectively). The final pregnancy rate did not differ between treatments (80.9%). In conclusion, a 12-day interval from the end of the puberty induction protocol to the start of the TAI protocol resulted in greater conception and pregnancy rates in prepubertal Nellore heifers.

Best protocol for controlled ovarian hyperstimulation in assisted reproductive technologies: fact or opinion?

From the early ages of assisted reproductive technologies (ARTs), different protocols have been developed with different gonadotropin preparations at different dosages with or without gonadotropin releasing hormone agonist or antagonist cotreatment. Various adjuvants have also been incorporated in controlled ovarian hyperstimulation (COH) protocols in an attempt to increase the efficacy and safety. The "best" protocol for COH should minimize stimulation burden while maintain the highest healthy, singleton, term live birth rates. Understandably, the one that meets all these expectations may not exist and COH should be individualized. Currently, there are worldwide differences in COH protocols and gonadotropin dose algorithms used depending on the country, demographics, funding stream, and existing guidelines/legislations. In 2014, despite efforts to individualize COH, currently, many of the protocols employ lack of high-quality evidence-based data. The aim of this review is to overview the efficacy and safety of available COH protocols, in normal responders, poor responders, and hyperresponders from evidence-based medicine perspective.