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Human Reproduction (Oxford, England) May 2023Does a short interval (i.e. ≤90 min), compared to a long interval (i.e. ≥180 min), between semen collection and intrauterine insemination (IUI) increase the... (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY QUESTION
Does a short interval (i.e. ≤90 min), compared to a long interval (i.e. ≥180 min), between semen collection and intrauterine insemination (IUI) increase the cumulative chance of an ongoing pregnancy after six IUI cycles?
SUMMARY ANSWER
A long interval between semen collection and IUI resulted in a borderline significant improvement in cumulative ongoing pregnancies and a statistically significant shorter time to pregnancy.
WHAT IS KNOWN ALREADY
Retrospective studies assessing the effect of the time interval between semen collection and IUI on pregnancy outcomes have shown inconclusive results. Some studies have indicated a beneficial effect of a short interval between semen collection and IUI on IUI outcomes, while others have not found any differences. To date, no prospective trials have been published on this subject.
STUDY DESIGN, SIZE, DURATION
The study was performed as a non-blinded, single-center RCT with 297 couples undergoing IUI treatment in a natural or stimulated cycle. The study was conducted between February 2012 and December 2018.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Couples with unexplained or mild male subfertility and an indication for IUI were randomly assigned for up to six IUI cycles into either the control group (long interval, i.e. 180 min or more between semen collection and insemination) or the study group (short interval, i.e. insemination as soon as possible after semen processing and within 90 min of semen collection). The study was carried out in an academic hospital-based IVF center in the Netherlands. The primary endpoint of the study was ongoing pregnancy rate per couple, defined as a viable intrauterine pregnancy at 10 weeks after insemination.
MAIN RESULTS AND THE ROLE OF CHANCE
In the short interval group, 142 couples were analyzed versus 138 couples in the long interval group. In the intention-to-treat (ITT) analysis, the cumulative ongoing pregnancy rate was significantly higher in the long interval group (71/138; 51.4%) compared to that in the short interval group (56/142; 39.4%; relative risks 0.77; 95% CI 0.59-0.99; P = 0.044). The time to pregnancy was significantly shorter in the long interval group (log-rank test, P = 0.012). A Cox regression analysis showed similar results (adjusted hazard ratio 1.528, 95% CI 1.074-2.174, P = 0.019).
LIMITATIONS, REASONS FOR CAUTION
Limitations of our study are the non-blinded design, the long inclusion and follow-up period of nearly seven years and the large number of protocol violations, especially because they predominantly occurred in the short interval group. The non-significant results in the per-protocol (PP) analyses and the weaknesses of the study should be taken into account in the assessment of the borderline significance of the results in the ITT analyses.
WIDER IMPLICATIONS OF THE FINDINGS
Because it is not necessary to perform the IUI immediately after semen processing, there can be more time available to choose the optimum work-flow and clinic occupancy. Clinics and laboratories should find their optimal timing of insemination, considering the time between human chorionic gonadotropin injection and insemination in relation to the sperm preparation techniques used as well as the storage time and conditions until insemination.
STUDY FUNDING/COMPETING INTEREST(S)
There were no external funding and no competing interests to declare.
TRIAL REGISTRATION NUMBER
Dutch trial registry, trial registration number NTR3144.
TRIAL REGISTRATION DATE
14 November 2011.
DATE OF FIRST PATIENT’S ENROLLMENT
5 February 2012.
Topics: Pregnancy; Female; Male; Humans; Retrospective Studies; Semen; Fertilization in Vitro; Pregnancy Rate; Insemination; Insemination, Artificial
PubMed: 36892580
DOI: 10.1093/humrep/dead044 -
Scientific Reports Aug 2019Somatic cell nuclear transfer (SCNT) technology provides an opportunity to multiply superior animals that could speed up dissemination of favorable genes into the...
Somatic cell nuclear transfer (SCNT) technology provides an opportunity to multiply superior animals that could speed up dissemination of favorable genes into the population. In the present study, we attempted to reproduce a superior breeding bull of Murrah buffalo, the best dairy breed of buffalo, using donor cells that were established from tail-skin biopsy and seminal plasma. We studied several parameters such as cell cycle stages, histone modifications (H3K9ac and H3K27me3) and expression of developmental genes in donor cells to determine their SCNT reprogramming potentials. We successfully produced the cloned bull from an embryo that was produced from the skin-derived cell. Growth, blood hematology, plasma biochemistries, and reproductive organs of the produced cloned bull were found normal. Subsequently, the bull was employed for semen production. Semen parameters such as CASA (Computer Assisted Semen Analysis) variables and in vitro fertilizing ability of sperms of the cloned bull were found similar to non-cloned bulls, including the donor bull. At present, we have 12 live healthy progenies that were produced using artificial insemination of frozen semen of the cloned bull, which indicate that the cloned bull is fertile and can be utilized in the buffalo breeding schemes. Taken together, we demonstrate that SCNT can be used to reproduce superior buffalo bulls.
Topics: Animals; Breeding; Buffaloes; Cloning, Organism; Epigenesis, Genetic; Fertility; Insemination, Artificial; Male; Nuclear Transfer Techniques; Semen; Semen Analysis; Semen Preservation
PubMed: 31388074
DOI: 10.1038/s41598-019-47909-8 -
Journal of Dairy Science Jul 2023This study aimed to determine the effect of 2 simple breeding strategies combining artificial insemination (AI) after detection of estrus (AIED) and timed AI (TAI) on...
Presynchronization with prostaglandin F and gonadotropin-releasing hormone simultaneously improved first-service pregnancy per artificial insemination in lactating Holstein cows compared with Presynch-14 when combined with detection of estrus.
This study aimed to determine the effect of 2 simple breeding strategies combining artificial insemination (AI) after detection of estrus (AIED) and timed AI (TAI) on first-service fertility in lactating Holstein cows. Weekly, lactating Holstein cows (n = l,049) between 40 and 46 d in milk (DIM) were randomly assigned to initiate 1 of 2 breeding strategies for first service: Presynch-14 and PG+G. Presynch-14 is a presynchronization strategy with 2 PGF treatments 14 d apart with the last PGF 14 d before the initiation of the Ovsynch protocol. Cows treated with PG+G receive a simpler presynchronization program that uses PGF and GnRH simultaneously 7 d before Ovsynch. In both treatments, cows detected in standing estrus by tail chalk at any time ≥55 DIM were inseminated, and treatment was discontinued (n = 525). Cows completing treatment received TAI from 78 to 84 DIM (n = 526). In a subgroup of cows that received TAI, blood was collected (n = 163) to assess circulating concentrations of progesterone, and ultrasonographic evaluations of ovaries were performed on the day of first GnRH of Ovsynch (n = 162) and PGF of Ovsynch (n = 122). The proportion of cows that received TAI was greater for PG+G compared with Presynch-14 (63.5 vs. 31.9%), which increased DIM at first service for cows treated with PG+G compared with Presynch-14 (75.5 ± 0.4 vs. 68.7 ± 0.4). For cows receiving TAI, the ovulatory response to first GnRH of Ovsynch (73.8 vs. 48.8%) and the proportion of cows with functional corpora lutea (92.6 vs. 73.1%) were greater for PG+G than Presynch-14. Cows treated with PG+G had greater overall pregnancy per AI (P/AI) 42 ± 7 d after AI (40.2 vs. 33.6%) and calving per AI (32.1 vs. 25.2%) than Presynch-14. For cows receiving AIED, treatment did not affect P/AI 42 ± 7 d after AI. However, for cows receiving TAI, PG+G increased P/AI compared with Presynch-14 (44.6 vs. 35.2%). Overall, cows receiving TAI had greater P/AI 42 ± 7 d after AI (42.5 vs. 31.5%) and calving per AI (34.1 vs. 23.7%) and decreased pregnancy loss (16.8 vs. 25.2%) than cows receiving AIED. In summary, PG+G increased the proportion of cows receiving TAI and the DIM at first service, P/AI, and calving per AI compared with Presynch-14 when both TAI programs were combined with AIED.
Topics: Pregnancy; Female; Cattle; Animals; Gonadotropin-Releasing Hormone; Lactation; Estrus Synchronization; Dinoprost; Estrus; Progesterone; Insemination, Artificial
PubMed: 37164866
DOI: 10.3168/jds.2022-22651 -
BioMed Research International 2022Polycystic ovary syndrome (PCOS) is the major reason for women's low fertility and the most frequent endocrine disorder in women of childbearing age. Homocysteine is an...
BACKGROUND
Polycystic ovary syndrome (PCOS) is the major reason for women's low fertility and the most frequent endocrine disorder in women of childbearing age. Homocysteine is an amino acid that contains sulfur that has been negatively correlated with the reproductive outcome of polycystic women treated with IVF/ICSI. However, the impact of blood homocysteine levels on the outcome of artificial insemination in polycystic ovary syndrome women is unknown. The goal of this study is to examine the impact of serum homocysteine on the result of intrauterine insemination in females who have polycystic ovary syndrome (PCOS).
METHODS
96 infertile women (129 cycles) treated with artificial insemination were collected, including 66 cases (87 cycles) in the case group (PCOS group) and 30 cases (42 cycles) in the control group (male factor infertility). The differences in general data amongst two groups, such as BMI, Hcy, and age, were compared. The case group has been classified into two groups based on serum Hcy level: LHcy group (Hcy < 15) and HHcy group (Hcy ≥ 15). The relationship among pregnancy and serum Hcy level outcome in PCOS women was compared.
RESULTS
The PCOS group had substantially increased serum homocysteine levels in comparison to the control group ( = 0.019). Among PCOS women, the clinical pregnancy rates of artificial insemination in the HHcy group and LHcy group were 14.29% and 37.88%. The difference among the two groups was substantial ( = 0.044). Artificial insemination frequency, ovulation induction, BMI, infertility years, AMH, serum testosterone, HOME IR, TSH, TPOAb, hCG, daily follicle size, intimal thickness, and other factors did not differ greatly between the two groups.
CONCLUSION
Serum homocysteine levels are increased in women having PCOS. Their levels above the threshold will lower the clinical pregnancy rate of intrauterine insemination in PCOS women.
Topics: Female; Homocysteine; Humans; Infertility, Female; Insemination, Artificial; Male; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy
PubMed: 36046438
DOI: 10.1155/2022/6311419 -
Biology of Reproduction Aug 2022Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport....
Sialic acid occupies terminal positions on O-glycans of cervical mucins, where they contribute to the increased viscosity of mucin thereby regulating sperm transport. This study characterized the sialylated cervical mucins from follicular phase mucus of six European ewe breeds with known differences in pregnancy rates following cervical artificial insemination (AI) using frozen-thawed semen at both synchronized and natural estrus cycles. These were Suffolk (low fertility) and Belclare (medium fertility) in Ireland, Ile de France and Romanov (both with medium fertility) in France, and Norwegian White Sheep (NWS) and Fur (both with high fertility) in Norway. Expression of mucin and sialic acid related genes was quantified using RNA-sequencing in cervical tissue from Suffolk, Belclare, Fur, and NWS only. Cervical tissue was also assessed for the percentage of cervical epithelial populated by mucin secreting goblet cells in the same four ewe breeds. Biochemical analysis showed that there was an effect of ewe breed on sialic acid species, which was represented by Suffolk having higher levels of Neu5,9Ac2 compared with NWS (P < 0.05). Suffolk ewes had a lower percentage of goblet cells than Fur and NWS (P < 0.05). Gene expression analysis identified higher expression of MUC5AC, MUC5B, ST6GAL1, and ST6GAL2 and lower expression of ST3GAL3, ST3GAL4, and SIGLEC10 in Suffolk compared with high fertility ewe breeds (P < 0.05). Our results indicate that specific alterations in sialylated mucin composition may be related to impaired cervical sperm transport.
Topics: Animals; Female; Fertility; Insemination, Artificial; Male; N-Acetylneuraminic Acid; Pregnancy; Pregnancy Rate; Semen; Semen Preservation; Sheep
PubMed: 35470857
DOI: 10.1093/biolre/ioac077 -
Journal of Dairy Science Jul 2022The objectives of this study were to determine the effects of nerve growth factor-β (NGF), purified from bulls' seminal plasma and administered at the time of...
The objectives of this study were to determine the effects of nerve growth factor-β (NGF), purified from bulls' seminal plasma and administered at the time of artificial insemination (AI), on progesterone post-AI, interferon-stimulated genes (ISG), and pregnancy per AI (P/AI) for lactating Holstein dairy cows enrolled in a timed-AI protocol. We hypothesized that administration of NGF at the time of AI would increase plasma progesterone post-AI, upregulate relative abundance of ISG, and improve P/AI in lactating dairy cows. Holstein cows (n = 557) from a single commercial dairy farm were blocked by parity and randomly assigned to receive an intramuscular injection containing 296 µg of bovine purified NGF at the time of AI, diluted in 2 mL of phosphate-buffered saline (NGF: n = 275), or receive only the 2 mL of phosphate-buffered saline (control: n = 282). Plasma progesterone and corpus luteum size were assessed in a subset of cows (NGF: n = 32; control: n = 36) at d 7, 14, and 19 post-AI. Relative mRNA abundance of ISG (ISG15, MX1, MX2, and RTP4) was assessed in peripheral blood leukocytes on d 19 post-AI. Pregnancy diagnosis was performed at 37 and 65 d post-AI. There was an interaction effect between treatment and parity for plasma progesterone; however, plasma progesterone and ISG did not differ between treatments. There were no effects of NGF for P/AI at 37 d post-AI (NGF = 40.0% vs. control = 41.6%), 65 d post-AI (NGF = 36.0% vs. control = 38.1%), and for pregnancy loss (NGF = 8.4% vs. control = 7.7%). The current study revealed that effects to NGF in lactating Holstein cows were minor and contingent with parity for progesterone, and no improvement in ISG relative abundance and P/AI were observed.
Topics: Animals; Cattle; Clinical Trials, Veterinary as Topic; Dinoprost; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Lactation; Male; Nerve Growth Factor; Phosphates; Pregnancy; Progesterone
PubMed: 35637004
DOI: 10.3168/jds.2022-21874 -
Fertility and Sterility Dec 2021To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates...
OBJECTIVE
To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred.
DESIGN
Retrospective cohort study.
SETTING
A university-based reproductive endocrinology and infertility clinic.
PATIENT(S)
Retrospective review of 1,957 IUI cycles performed on 660 patients between July 2007 and May 2012.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
The primary outcome was live birth. Secondary outcomes were positive serum pregnancy result and clinical pregnancy. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient.
RESULT(S)
Live birth rates were similar in IUI cycles with and without regurgitation (6.3% vs. 6.8%, respectively, RR = 0.82, 95% CI [0.53-1.26]). Clinical pregnancy rates in the presence or absence of regurgitation were 10.5% vs. 10.0% (RR = 0.99, 95% CI [0.73-1.35]). Positive serum pregnancy tests after IUI did not differ by regurgitation status (15.0% vs. 15.4%, RR = 0.97, 95% CI [0.75-1.24]). Results were unchanged when adjusted for covariates (age, race and ethnicity, body mass index, duration of infertility, medication, infertility diagnosis, total motile count, and method of sperm preparation).
CONCLUSION(S)
The presence of regurgitation during the IUI procedure is not related to pregnancy outcome.
Topics: Adult; Cohort Studies; Female; Fertilization in Vitro; Humans; Insemination, Artificial; Live Birth; Pregnancy; Pregnancy Rate; Retrospective Studies; Semen
PubMed: 34417056
DOI: 10.1016/j.fertnstert.2021.07.1183 -
Journal of Dairy Science Dec 2020The objective was to use ovulation synchronization with timed artificial insemination (TAI) to evaluate the effect of timing of artificial insemination (AI) with frozen...
Evaluation of delayed timing of artificial insemination with sex-sorted sperm on pregnancy per artificial insemination in seasonal-calving, pasture-based lactating dairy cows.
The objective was to use ovulation synchronization with timed artificial insemination (TAI) to evaluate the effect of timing of artificial insemination (AI) with frozen sex-sorted sperm on fertility performance in pasture-based compact calving herds. Ejaculates from 3 Holstein-Friesian bulls were split and processed to provide frozen sex-sorted sperm (SS) at 4 × 10 sperm per straw, and frozen conventional sperm at 15 × 10 sperm per straw (CONV). A modified Progesterone-Ovsynch protocol was used for estrous synchronization, with TAI occurring 16 h after the second GnRH injection for cows assigned to CONV, and either 16 h (SS-16) or 22 h (SS-22) for cows assigned to SS. Pregnancy diagnosis was conducted by transrectal ultrasound scanning of the uterus 35 to 40 d after TAI (n = 2,175 records available for analysis). Generalized linear mixed models were used to examine the effects of treatment on pregnancy per artificial insemination (P/AI). Fixed effects included treatment (n = 3), bull (n = 3), treatment by bull interaction, parity (n = 4), days-in-milk category (n = 3), and treatment by days-in-milk category, with herd (n = 24) included as a random effect. Pregnancy per AI was greater for CONV compared with both SS-16 and SS-22 (61.1%, 49.0%, and 51.3%, respectively), and the SS treatments did not differ from each other (relative P/AI for SS-16 and SS-22 vs. CONV were 80.2% and 84.0%, respectively). There were significant bull and treatment by bull interaction effects. Additional analysis was undertaken using a model that included herd as a fixed effect. This analysis identified marked herd-to-herd variation (within-herd relative P/AI for the combined SS treatments vs. CONV ranged from 48-121%). The tertile of herds with the best performance achieved a mean relative P/AI of 100% (range = 91-121%), indicating that P/AI equivalent to CONV is achievable with SS. Conversely, the tertile of herds with the poorest performance achieved a mean relative P/AI of 67% (range = 48-77%). We found that SS resulted in poorer overall P/AI compared with CONV sperm regardless of timing of AI. Marked variation existed between herds; however, one-third of herds achieved P/AI results equal to CONV. Identification of factors responsible for the large herd-to-herd variation in P/AI with SS, and development of strategies to reduce this variation, warrant further research.
Topics: Animals; Cattle; Estrus; Estrus Synchronization; Female; Fertility; Freezing; Gonadotropin-Releasing Hormone; Insemination, Artificial; Lactation; Linear Models; Male; Milk; Ovulation; Parity; Pregnancy; Progesterone; Seasons; Sex Determination Processes; Spermatozoa; Time Factors
PubMed: 33069411
DOI: 10.3168/jds.2020-18847 -
Journal of Dairy Science Feb 2020One strategy for improving fertility in cattle is administration of GnRH or human chorionic gonadotropin (hCG) during the luteal phase, which increases progesterone (P4)... (Meta-Analysis)
Meta-Analysis
Association of pregnancy per artificial insemination with gonadotropin-releasing hormone and human chorionic gonadotropin administered during the luteal phase after artificial insemination in dairy cows: A meta-analysis.
One strategy for improving fertility in cattle is administration of GnRH or human chorionic gonadotropin (hCG) during the luteal phase, which increases progesterone (P4) secretion and delays luteolysis. To provide an overview of how GnRH or hCG treatment between 4 and 15 d after artificial insemination (AI) improves pregnancy per AI (P/AI) in cows, a meta-analysis was performed on 107 different trials from 52 publications. Data from 18,082 treated cows and 18,385 untreated controls were meta-analyzed. The meta-analysis explained the relative risk for P/AI with GnRH or hCG treatment under various circumstances. The results did not show any difference in P/AI between cows treated with hCG and cows treated with GnRH. Compared with no treatment, treatment with GnRH or hCG improved the chances of P/AI in cows with very poor (<30%) and poor (30.1 to 45%) fertility, whereas treatment did not benefit cows with very good fertility (>60.1%). Moreover, treatment with GnRH and hCG improved the chances of P/AI in primiparous cows. The improvement was much better in primiparous cows with very low fertility. Treatment with buserelin at a dose above 10 µg and with hCG at a dose above 2,500 IU was associated with increased chances of P/AI compared with lower doses. Treatment with GnRH 10 d after AI was also associated with increased chances of P/AI compared with earlier treatment. The present meta-analysis showed that the use of GnRH and hCG after AI should be focused on cows expected to have low or moderate fertility. Day and dose of treatment have to be considered as well.
Topics: Animals; Buserelin; Cattle; Chorionic Gonadotropin; Dairying; Female; Fertility; Gonadotropin-Releasing Hormone; Humans; Insemination, Artificial; Luteal Phase; Luteolysis; Pregnancy; Progesterone; Time Factors
PubMed: 31785879
DOI: 10.3168/jds.2019-16439 -
Journal of Dairy Science Sep 2019The reproductive parameters of dairy cattle have continuously declined worldwide over the last 50 years. Nutritional imbalances are identified as risk factors for this...
The reproductive parameters of dairy cattle have continuously declined worldwide over the last 50 years. Nutritional imbalances are identified as risk factors for this decrease of reproductive performance. The present paper aims to quantify the decrease in the pregnancy per artificial insemination (P/AI) in the case of high milk ketones before and after AI. A total of 388,731 test-day from the Brittany Milk Recording Program in France from 226,429 cow-lactations were provided for this trial. For each test-day, information about lactation characteristics, date of AI, date of the following calving, and acetone and β-hydroxybutyrate (BHB) values were included. Ketones were predicted by Fourier transform mid-infrared spectroscopy using MilkoScan Foss analyzers (Foss, Hillerød, Denmark). Many thresholds were evaluated to define cows with hyperketolactia. Hyperketolactia statuses were then categorized into 1 of 4 possible classes according to the milk ketone dynamics for each AI and each threshold of acetone or BHB values (low-low, high-low, low-high, and high-high) within 20 d before and after AI. Similarly, the dynamics of udder health were characterized by changes in somatic cell counts measured at the same test day as ketone bodies. A logistic regression with a Poisson correction was performed to explain the relationship of P/AI with milk ketones and somatic cell count dynamics. Predicted acetone and BHB ranged from -0.51 to 4.92 mM (mean = 0.08 mM, SD = 0.10 mM) and -0.62 to 5.85 mM (mean = 0.07 mM, SD = 0.1 mM), respectively. Hyperketolactia defined by high acetone levels before AI was not associated with decreased P/AI, but high acetone levels after AI were associated with a >10% reduction in P/AI for all thresholds >0.10 mM. Hyperketolactia, defined by high BHB values before, after, or before and after AI, was associated with a 6 to 14% reduction in P/AI compared with cows with low BHB values. These associations are lower than those reported in previous trials in which blood ketones were used. High ketones in advanced lactation are likely to be the result of various primary disorders (secondary ketosis). Because the present work demonstrated that this situation is considered a risk factor for deteriorated reproductive performance, we suggest that high ketones in early and advanced lactation should be of interest to farm advisors.
Topics: 3-Hydroxybutyric Acid; Animals; Cattle; Female; Insemination, Artificial; Ketones; Lactation; Milk; Pregnancy; Pregnancy Rate; Treatment Outcome
PubMed: 31326183
DOI: 10.3168/jds.2019-16477