Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization.

OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Effect of reproductive management programs that prioritized artificial insemination at detected estrus or timed artificial insemination on the economic performance of primiparous Holstein cows of different genetic merit for fertility.

The objective of this randomized controlled experiment was to evaluate the effect of reproductive management programs that prioritized artificial insemination (AI) at detected estrus (AIE) or timed AI (TAI) during the first lactation on the economic performance of dairy cows of different genomically enhanced predicted transmitting ability for fertility. Lactating primiparous Holstein cows from 6 commercial farms were stratified into high, medium, and low fertility groups based on a reproduction index value calculated from multiple genomically enhanced predicted transmitting abilities to predict the number of days to achieve pregnancy. Within herd and fertility group, cows were randomly assigned either to a program that prioritized AIE (P-AIE; n = 1,416) and used TAI for cows not AIE for all AI services or another that prioritized TAI and had an extended voluntary waiting period for first service and prioritized TAI for second and greater AI services (P-TAI; n = 1,338). Cash flow (CF) per cow accumulated for the experimental (first) and second calving interval (CIN) and cash flow per slot per 28 mo after calving in the experimental lactation were calculated. Market and rearing heifer cost values were used for estimating CF. For cows in the high fertility group, a positive effect of delayed pregnancy on milk income during the first lactation was observed (+$248 for P-TAI) but was insufficient to generate significant differences in CF between treatments mainly because of milk income compensation in the second lactation (+$125 for P-AIE) and minor reductions in reproductive cost and gains in calf value for the P-AIE treatment. In this regard, CF for 2 CIN was greater for the P-TAI treatment by $61 and $86 for market and rearing replacement heifer cost, respectively. Similarly, CF per slot was favorable to the P-TAI treatment but only by $13 and $47 for market and rearing replacement heifer cost, respectively. For cows in the low fertility group, CF was numerically in favor of the P-AIE treatment due to a pregnancy and herd exit dynamics that resulted in gains in milk income over feed cost during the first ($29) and second ($113) lactation. Differences in CF for the 2 CIN were $58 and $47 for market or rearing heifer value, respectively, and $77 and $19 for market and rearing heifer values, respectively for the slot analysis. Differences in CF between cows of different genetic merit for fertility were consistent across treatment and estimation method. Of note, cows in the low fertility group had greater CF than cows in the high fertility group in all comparisons, ranging from $198 per cow for 2 CIN to as much as $427 per slot. For the low fertility group, greater milk production contributed directly (milk income over feed cost) and indirectly (reduced culling) to increased CF. We concluded that genetic merit for fertility and CF are associated because cows of inferior genetic potential for fertility had greater CF than cows of superior genetic for fertility despite some increased costs and reduced revenues. Also, the magnitude of the CF differences observed for cows of different genetic merit for fertility managed with the P-AIE or P-TAI program may be valuable to commercial dairy farms but did not allow to conclusively support the choice of a type of reproductive management strategy for cows of different genetic merit for fertility.

Monitoring of health status, performance and transcript abundance of some genes in dairy heifers produced by embryo transfer or artificial insemination.

The use of multiple ovulation and embryo transfer (MOET) technology in the dairy cattle industry has increased dramatically in recent decades for the production of offspring from genetically superior cows. Yet, its long-term ramifications on adult performance have not been adequately clarified. Therefore, this study targeted comparing dairy heifers born after the transfer of in vivo-produced embryos (MOET-heifers, n = 400) and those born after artificial insemination (AI-heifers, n = 340). The performance of MOET-heifers and AI-heifers was compared from birth till completion of the first lactation regarding health, fertility and some lactational performance parameters. The transcript abundance of several genes was also assessed in peripheral blood leukocytes (PBWC). Results showed greater pre-weaning mortalities, greater likelihood of being culled as a nulliparous heifer and younger age at first insemination in AI-heifers (p < .001). At their first calving, primiparous MOET-heifers experienced a greater (p < .01) incidence of stillbirth compared to primiparous AI-heifers. In spite of that, primiparous AI-heifers were more likely to be culled due to infertility (p < .001), took a greater number of inseminations to achieve pregnancy (p < .01) and displayed a longer first calving interval. There was a similar lactational performance between the two groups. Upregulation of the transcript levels of TAC3, LOC522763, TFF2, SAXO2, CNKSR3 and ALAS2 was interestingly observed in primiparous MOET-heifers, compared to primiparous AI-heifers. In conclusion, MOET-heifers were less likely to be culled during the first year of life, had superior reproductive performance versus AI-heifers during their first lactation and expressed upregulation of genes associated with fertility.

A stochastic animal life cycle simulation model for a whole dairy farm system model: Assessing the value of combined heifer and lactating dairy cow reproductive management programs.

This analysis introduces a stochastic herd simulation model and evaluates the estimated reproductive and economic performance of combinations of reproductive management programs for both heifers and lactating cows. The model simulates the growth, reproductive performance, production, and culling for individual animals and integrates individual animal outcomes to represent herd dynamics daily. The model has an extensible structure, allowing for future modification and expansion, and has been integrated into the Ruminant Farm Systems model, a holistic dairy farm simulation model. The herd simulation model was used to compare outcomes of 10 reproductive management scenarios based on common practices on US farms with combinations of estrous detection (ED) and artificial insemination (AI), synchronized estrous detection (synch-ED) and AI, timed AI (TAI, 5-d CIDR-Synch) programs for heifers; and ED, a combination of ED and TAI (ED-TAI, Presynch-Ovsynch), and TAI (Double-Ovsynch) with or without ED during the reinsemination period for lactating cows. The simulation was run for a 1,000-cow (milking and dry) herd for 7 yr, and we used the outcomes from the final year to evaluate results. The model accounted for incomes from milk, sold calves, and culled heifers and cows, as well as costs from breeding, AI, semen, pregnancy diagnosis, and calf, heifer, and cow feed. We found that the interaction between heifer and lactating dairy cow reproductive management programs influences herd economic performance primarily due to heifer rearing costs and replacement heifer supply. The greatest net return (NR) was achieved when combining heifer TAI and cow TAI without ED during the reinsemination period, whereas the lowest NR was obtained when combining heifer synch-ED with cow ED.

An agent-based simulation model to compare different reproductive strategies in cow-calf operations: Economic performance.

In a companion paper, Ojeda-Rojas et al. (2021) [1] describe a stochastic agent-based simulation (ABS) model of a cow-calf operation on a commercial farm in São Paulo, Brazil. The model's parameterization was based on data collected from two sources: a real beef cattle herd and related scientific literature. Based on the mentioned simulation model, this study aims to assess the economic outcome of 10 different reproductive scenarios: Natural mating only (ONM); one timed artificial insemination (TAI) plus natural mating (NM) (1TAI + NM); two TAI plus NM, with 24, 32, and 40 days between TAI (2TAI/24 + NM, 2TAI/32 + NM, and 2TAI/40 + NM, respectively); three TAI without NM, with 24, 32, and 40 days between TAI (3TAI/24, 3TAI/32, and 3TAI/40, respectively); and three TAI plus NM, with an interval between TAI of 24 (3TAI/24 + NM) and 32 days (3TAI/32 + NM). The simulation was performed on an animal-by-animal basis over a time horizon of 5000 days. Each scenario had 32 farms, and each farm kept up to 400 adult females. According to the scenario, a bull population was composed of 0, 7, or 15 individuals. The outcomes, represented as means ± standard deviations, were assessed after reaching a steady-state (1825 days). The model outcomes showed that the 3TAI/24 + NM scenario resulted in higher incomes (US$ 96,479.19 ± 709.81), whereas the ONM scenario had the lowest incomes (US$ 79,753.37 ± 741.87). The 3TAI/24 + NM (US$ 101.720.63 ± 79.21) and ONM (US$ 90.898.58 ± 59.17) scenarios presented the highest and lowest total operating costs (TOC), respectively. However, when TOC was evaluated per kg of the weaned calf, the highest and lowest costs were associated with the ONM (US$ 2.81 ± 0.03/kg) and 2TAI/24 + NM (US$ 2.17 ± 0,04/kg) scenarios, respectively. Our model suggests that reproductive strategies that use TAI have a better economic performance than those under NM. However, when performing three TAI with an interval of 40 days, the benefit was lower; in some cases, it was even worse than the ONM. Combining TAI with early pregnancy diagnosis resulted in better economic performance than other TAI programs and NM. The 2TAI/24 + NM scenario outperformed the others due to the contrast between its high income and moderate costs. Beef cattle production is a highly complex system. Simulations models, specifically ABS models, could make the decision-making process on complex systems straightforward and effective. Furthermore, ABS models can overcome the limitations of conventional research approaches, such as high costs and long experimentation periods.

Timed artificial insemination in crossbred mares: Reproductive efficiency and costs.

Timed artificial insemination (TAI) has boosted the use of conventional artificial insemination (CAI) by employing hormonal protocols to synchronize oestrus and ovulation. This study aimed to evaluate the efficiency of a hormonal protocol for TAI in mares, based on a combination of progesterone releasing intravaginal device (PRID), prostaglandin (PGF2α ) and human chorionic gonadotropin (hCG); and compare financial costs between CAI and TAI. Twenty-one mares were divided into two groups: CAI group (CAIG; n = 6 mares; 17 oestrous cycles) and TAI group (TAIG; n = 15 mares; 15 oestrous cycles). The CAIG was subjected to CAI, involving follicular dynamics and uterine oedema monitoring with ultrasound examinations (US), and administration of hCG (1,600 IU) when the dominant follicle (DF) diameter's ≥35 mm + uterine oedema + cervix opening. The AI was performed with fresh semen (500 × 106 cells), and embryo was recovered on day 8 (D8) after ovulation. In TAI, mares received 1.9 g PRID on D0. On D10, PRID was removed and 6.71 mg dinoprost tromethamine was administered. Ovulation was induced on D14 (1,600 IU of hCG) regardless of the DF diameter's, and AI was performed with fresh semen (500 × 106 cells). On D30 after AI, pregnancy was confirmed by US. The pregnancy rate was 80.0% in TAIG and 82.3% in CAIG (p > .05). The TAI protocol resulted in 65% reduction in professional transport costs, and 40% reduction in material costs. The TAI was as efficient as CAI, provided reduction in costs and handlings, and is recommended in mares.

Assessment of ovulation synchronization protocols in goats and use of pregnancy specific protein B (PSPB) enzyme linked immunsorbent assay (ELISA) to determine kid number at birth.

The efficacy of several protocols for ovulation synchronization and timed artificial insemination (TAI) in goats was examined. In addition, the relationship between levels of pregnancy specific protein B (PSPB) during gestation assessed with a commercially available ELISA and the number of offspring at birth was determined. In Experiment 1, 70 does were randomized into four treatments: (1) breed by estrus [BBE], (2) 6-d treatment with a new [C6N], (3) once-used [C61], or (4) twice-used Controled Internal Drug Release (CIDR) device [C62)]. BBE does received two 15 mg doses of prostaglandin-F2α (PGF) at a 10-d interval and were bred 12 h after estrus onset. CIDR groups received a CIDR for 6 d with 15 mg PGF given at CIDR removal. TAI was performed 48 h after CIDR removal and does were given 50 µg GnRH. All does were inseminated with a single dose of frozen semen using a non-surgical, transcervical technique. Pregnancy rates for the BBE, C6N, C61 and C62 treatment groups were 39% ± 12%, 64% ± 12%, 77% ± 12% and 57% ± 12%, respectively, and did not differ. Reuse of CIDRs, even with reuse extending for a total of 21 d, was as effective as new CIDRs for synchronization of ovulation. In Experiment 2, 68 does were randomized into four treatments: (1) BBE, (2) C6N, (3) NC.Synch [NCS], (4) modified NCS [NCSM]. The BBE and C6N groups were as described for Experiment 1. The NCS and NCSM groups received 15 mg PGF on Day 1, 50 µg GnRH on Day 8 and 15 mg PGF on Day 15 (NCS) or Day 15.5 (NCSM). Does were bred by TAI at 72 h (NCS) or 60 h (NCSM) after the second PGF injection. All does in the NCS and NCSM groups received 50 µg GnRH at TAI. Pregnancy rates were 53% ± 12%, 30% ± 11%, 50% ± 11% and 41% ± 12% for does in the BBE, C6N, NCS and NCSM group, respectively, and did not differ. In Experiment 3, 62 does pregnant to TAI were bled at Days 48 and 85 post-insemination for PSPB. Data on kid numbers and birth weights were subsequently recorded. At Day 48 of gestation, PSPB levels for does birthing singletons were lower than for does birthing twins or triplets (25.0 ± 0.1a, 28.8 ± 0.1b and 30.7 ± 0b ng/mL, respectively, abP<0.05). At Day 85 of gestation, PSPB levels were progressively greater for does birthing singletons versus twins versus triplets (27.0 ± 0.1a, 28.5 ± 0.1b and 31.6 ± 0c ng/mL, abcP<0.05). In conclusion, PSPB concentrations detected using a commercially available ELISA at Day 48 or 85 of gestation could distinguish does carrying single versus multiple fetuses.

Growing body of evidence supports intrauterine insemination as first line treatment and rejects unfounded concerns about its efficacy, risks and cost effectiveness.

IUI has been practiced for five decades but only three unconvincing trials attempted to demonstrate the superiority of IUI over sexual intercourse (SI). In the absence of evidence of its effectiveness, the National Institute for Clinical Excellence (NICE) recommended IVF over IUI after 2 years of unprotected SI. High-quality recent data in well-constructed studies suggest that biases against IUI procedures and in favour of IVF are invalid. It is unethical to continue to misinform patients and stakeholders. The well-constructed randomised controlled trials (RCT) show IUI procedure to be efficient, with minimal risk, and above all improved cost-effectiveness when compared to IVF for live birth. IUI as first-line treatment should be offered to most patients, while funding agencies and stakeholders need to be urgently informed of the cost-benefit in offering IUI. Fertility clinics, IVF interest groups, and regulatory bodies should amend their patient information and guidance to state that IUI should be the first line treatment and that IVF should be offered only when essential. Reappraising and promoting IUI based on evidence enhances patient autonomy, choices, and trust, while allowing the fertility industry to operate within an ethical and acceptable framework not seen as exploitative toward vulnerable patients.

Misclassification in Assessment of First Trimester In-utero Exposure to Drugs Used Proximally to Conception: the Example of Letrozole Utilization for Infertility Treatment.

Letrozole is an aromatase inhibitor that has an unapproved use for ovulation induction with infertility. Because of the proximity of this use to conception, we selected letrozole to study the effect of 3 different methods for identifying the pregnancy start date and their impact on exposure misclassification. Using electronic health data from the US Sentinel database (2001-2015), we identified live-birth pregnancies conceived through in-vitro fertilization or intrauterine insemination. The pregnancy start was calculated using 1) a validated algorithm to estimate the last menstrual period (LMP), 2) LMP + 14 days (i.e., conception estimate), and 3) the fertility-procedure date. We identified 47,628 live-births after intrauterine insemination (n = 24,962) and in-vitro fertilization (n = 22,666), in which 2,458 (5.3%) mothers received letrozole. The algorithm-based conception estimate occurred within 14 days of the fertility procedure for 78.3% of pregnancies. Defining pregnancy start as LMP (45.7/1,000 pregnancies) or LMP + 14 days (12.7/1,000 pregnancies) overestimated letrozole exposure during pregnancy by 8.4-fold and 2.3-fold, respectively, compared with defining it at the date of the fertility procedure (5.5/1,000 pregnancies). While most studies of drug utilization in pregnancy use LMP as the conventional pregnancy start, this introduced substantial exposure misclassification in the example of letrozole. LMP + 14 days was less biased. Researchers should carefully consider the impact of the method for identifying the pregnancy start date on the potential for exposure misclassification.

Does intra-uterine insemination have a place in modern ART practice?

Intra-uterine insemination (IUI) is a cheaper, less intensive treatment modality for achieving a pregnancy in couples with specific indications. The use of IUI seems to have declined after NICE guideline 2013 (CG 156) recommended IVF over IUI in couples with unexplained and mild male factor infertility. This review examines the current evidence and the applicability of IUI as a first-line option of treatment in couples with unexplained and mild male factor subfertility. The outcome of the review supports this argument. It is likely that IUI will re-emerge as an effective treatment option and thereby increase the choice to patients. However, there is a need for ongoing research and investment into funding of good quality trials to improve and strengthen the evidence base.

Economic evaluation of sexed semen use in Iranian dairy farms according to field data.

In this study, at first, the reproductive consequences of sexed semen use were quantified and then the cost-benefit of sexed semen use on Iranian commercial dairy farms was evaluated. Retrospective data collected during 2006 to 2013 from four large dairy farms in the Isfahan province of Iran were used for this study. These data included of 13,003 heifers records, from which 11.2% used sexed semen from 33 different bulls. All data were analysed using a multivariable logistical regression model, GENMOD procedure from SAS software. The analyses included economic values (EVs) when sexed semen was used in 1, 2 and 3 consecutive services compared with conventional semen use for all insemination. Results showed that rates of female born from sexed semen (86.3%) were 1.8 times higher than those from conventional semen (48.5%). Conception rates were 43.8% for sexed and 59.2% for conventional semen (p < 0.0001). Abortion (4.4% vs. 5.4%) and stillbirth (8.4% vs. 7.2%) rates were not significantly different between sexed and conventional semen (p = 0.09). Dystocia rates were 15.5% for sexed and 19.6% for conventional semen (p = 0.002). Sexed semen use showed negative EVs through all investigated scenarios. The EVs from the implementation of 1, 2 and 3 sexed semen breedings were estimated to be $-6.69, $-14.01 and $-19.08, respectively. Total insemination cost and increased cost of age at first calving were the most important components associated with negative EV for sexed semen. Sensitivity analysis showed that proportion of conception rates of sexed semen to conventional semen and female calf value were the most important biological and economic factors influencing on the EV of sexed semen, respectively. Breakeven would be obtained with 77.4%-79.3% conception rates or female calf value of $719.5-$754.7 through investigated breeding scenarios when all other factors remained the same.

Economic performance of lactating dairy cows submitted for first service timed artificial insemination after a voluntary waiting period of 60 or 88 days.

The objective of this study was to evaluate the economic performance of dairy cows managed with a voluntary waiting period (VWP) of 60 or 88 d. A secondary objective was estimating variation in cash flow under different input pricing scenarios through stochastic Monte Carlo simulations. Lactating Holstein cows from 3 commercial farms were blocked by parity group and total milk yield in their previous lactation and then randomly assigned to a VWP of 60 (VWP60; n = 1,352) or 88 d (VWP88; n = 1,359). All cows received timed-artificial insemination (TAI) for first service after synchronization of ovulation with the Double-Ovsynch protocol. For second and greater services, cows received artificial insemination (AI) after detection of estrus or the Ovsynch protocol initiated 32 ± 3 d after AI. Two analyses were performed: (1) cash flow per cow for the calving interval of the experimental lactation and (2) cash flow per slot occupied by each cow enrolled in the experiment for an 18-mo period after calving in the experimental lactation. Extending the VWP from 60 to 88 d delayed time to pregnancy during lactation (∼20 d) and increased the risk of leaving the herd for multiparous cows (hazard ratio = 1.21). As a result, a smaller proportion of multiparous cows calved again and had a subsequent lactation (-6%). The shift in time to pregnancy combined with the herd exit dynamics resulted in longer lactation length for primiparous (22 d) but not multiparous cows. Longer lactations led to greater milk income over feed cost and a tendency for greater cash flow during the experimental lactation for primiparous but not multiparous cows in the VWP88 group. On the other hand, profitability per slot for the 18-mo period was numerically greater ($68 slot/18 mo) for primiparous cows but numerically reduced (-$85 slot/18 mo) for multiparous cows in the VWP88 treatment. For primiparous cows most of the difference in cash flow was explained by replacement cost, whereas for multiparous cows it was mostly explained by differences in replacement cost and income over feed cost. Under variable input pricing conditions generated through stochastic simulations, the longer VWP treatment always increased cash flow per 18 mo for primiparous and reduced cash flow for multiparous cows. In conclusion, extending the duration of the VWP from 60 to 88 d numerically increased profitability of primiparous cows and reduced profitability of multiparous cows. Such an effect depended mostly on the herd replacement dynamics and milk production efficiency.

IUI: review and systematic assessment of the evidence that supports global recommendations.

BACKGROUND: IUI with or without ovarian stimulation (OS) has become a first-line treatment option for many infertile couples, worldwide. The appropriate treatment modality for couples and their clinical management through IUI or IUI/OS cycles must consider maternal and perinatal outcomes, most notably the clinical complication of higher-order multiple pregnancies associated with IUI-OS. With a current global emphasis to continue to decrease maternal and perinatal mortality and morbidity, the World Health Organization (WHO) had established a multi-year project to review the evidence for the establishment of normative guidance for the implementation of IUI as a treatment to address fertility problems, and to consider its cost-effectiveness for lower resource settings. OBJECTIVE AND RATIONALE: The objective of this review is to provide a review of the evidence of 13 prioritized questions that cover IUI with and without OS. We provide summary recommendations for the development of global, evidence-based guidelines based upon methodology established by the WHO. SEARCH METHODS: We performed a comprehensive search using question-specific relevant search terms in May 2015. For each PICO (Population, Intervention, Comparison and Outcomes) drafted by WHO, specific search terms were used to find the available evidence in MEDLINE (1950 to May 2015) and The Cochrane Library (until May 2015). After presentation to an expert panel, a further hand search of references in relevant reviews was performed up to January 2017. Articles that were found to be relevant were read and analysed by two investigators and critically appraised using the Cochrane Collaboration's tool for assessing risk of bias, and AMSTAR in case of systematic reviews. The quality of the evidence was assessed using the GRADE system. An independent expert review process of our analysis was conducted in November 2016. OUTCOMES: This review provides an assessment and synthesis of the evidence that covers 13 clinical questions including the indications for the use of IUI versus expectant management, the sperm parameters required, the best and optimal method of timing and number of inseminations per cycle, prevention strategies to decrease multiple gestational pregnancies, and the cost-effectiveness of IUI versus IVF. We provide an evidence-based formulation of 20 recommendations, as well as two best practice points that address the integration of methods for the prevention of infection in the IUI laboratory. The quality of the evidence ranges from very low to high, with evidence that may be decades old but of high quality, however, we further discuss where critical research gaps in the evidence remain. WIDER IMPLICATIONS: This review presents an evidence synthesis assessment and includes recommendations that will assist health care providers worldwide with their decision-making when considering IUI treatments, with or without OS, for their patients presenting with fertility problems.

Cost-effectiveness of ovarian stimulation with gonadotrophin and clomiphene citrate in an intrauterine insemination programme for subfertile couples.

Ovarian stimulation with low-dose human menopausal gonadotrophin (HMG) is superior to clomiphene citrate in intrauterine insemination (IUI) cycles with respect to clinical pregnancy rate, but it is unclear whether HMG is also the more cost-effective option. The aim of this study was to compare the cost-effectiveness of ovarian stimulation with low-dose subcutaneously administred HMG (37.5-75 IU per day) to orally administred clomiphene citrate (50 mg/day from day 3-7) in an IUI programme for subfertile couples. A cost-effectiveness analysis was conducted using the results of a randomized trial, including 620 IUI cycles. The primary outcome was the incremental cost-effectiveness ratio (ICER) of using HMG versus clomiphene citrate. Results are presented from the healthcare payer perspective. The total cost per patient associated with one IUI treatment with HMG is €764, whereas it is €558 if clomiphene citrate is used, resulting in an incremental cost of €206 for HMG per treatment. The incremental clinical pregnancy rate of using HMG instead of clomiphene citrate, however, is also 5.7 percentage points higher, resulting in an ICER of HMG versus clomiphene citrate of €3615 per additional clinical pregnancy achieved. On average, HMG was found to be more cost-effective than clomiphene citrate.

The invention of artificial fertilization in the eighteenth and nineteenth century.

Artificial insemination and other fertilization techniques are today considered central to the history of reproductive medicine. The medical treatment of infertile couples, however, constitutes just a small part of the whole story of artificial fertilization. Lazzaro Spallanzani (1729-1799) in particular, said to have been the inventor of artificial insemination, did not develop this method for medical purposes. He belonged to a generation of naturalists to whom artificial insemination was part of a heterogeneous series of investigations that were undertaken to explore the natural history of animal generation. Questions concerning conception, the role of the gametes, the definition of species, the production of hybrids or livestock breeding were all included in these investigations. Thus, no one strain of thought, nor single set of ideas or interests, entirely shaped the development of artificial fertilization.

Contribution of semen trait selection, artificial insemination technique, and semen dose to the profitability of pig production systems: A simulation study.

The economic impact of selection for semen traits on pig production systems and potential interaction with artificial insemination (AI) technique and semen dose remains partially understood. The objectives of this study were to compare the financial indicators (gross return, net profit, cost) in a three-tier pig production system under one of two selection strategies: a traditional strategy including nine paternal and maternal traits (S9) and an advanced strategy that adds four semen traits (S13). Maternal traits included the number of pigs born alive, litter birth weight, adjusted 21-day litter weight, and the number of pigs at 21 days, and paternal traits included days to 113.5 kg, back fat, average daily gain, feed efficiency, and carcass lean percentage. The four semen traits included volume, concentration, progressive motility of spermatozoa, and abnormal spermatozoa. Simultaneously, the impact of two AI techniques and a range of fresh refrigerated semen doses including cervical AI with 3 × 10(9) (CAI3) and 2 × 10(9) (CAI2) sperm cells/dose, and intrauterine AI with 1.5 × 10(9) (IUI1.5), 0.75 × 10(9) (IUI0.75), and 0.5 × 10(9) (IUI0.5) sperm cells/dose were evaluated. These factors were also evaluated using a range of farrowing rates (60%-90%), litter sizes (8-14 live-born pigs), and a selected semen collection frequency. The financial impact of the factors was assessed through simulation of a three-way crossbreeding system (maternal nucleus lines A and B and paternal nucleus line C) using ZPLAN. The highest return on investment (profit/cost) of boars was observed at 2.33 collections/wk (three periods of 24 hours between collections). Under this schedule, a significant (P < 0.0001) interaction between the selection strategy and the AI technique-dose combination was identified for the gross return; meanwhile, significant (P < 0.0001) additive effects of the selection strategy and AI technique-dose combination were observed for the net profit. The highest gross return was obtained under S13 with IUI0.75 and IUI0.5. The net profit of S13 was 34.37% higher than the traditional S9 (P < 0.0001). The net profit favored IUI0.5 with relative differences of 4.13%, 2.41%, 1.72%, and 0.43% compared to CAI3, CAI2, IUI1.5, and IUI0.75, respectively. The advanced selection strategy proposed including four semen traits is recommended on the basis of the higher profitability relative to the traditional strategy.

Combined use of progesterone inserts, ultrasongraphy, and GnRH to identify and resynchronize nonpregnant cows and heifers 21 days after timed artificial insemination.

The objective was to decrease the reinsemination interval (RI) when dairy cows and heifers are inseminated using all timed artificial insemination (TAI) programs. Holstein cows (n = 211) and heifers (n = 153) were randomly assigned to a control or 21-day Resynch (21dRES) at 13 days after TAI. Animals in 21dRES (n = 109 cows and 77 heifers) had a progesterone device inserted on Day 13 and removed on Day 20 after TAI and ovaries scanned by ultrasonography. Animals found not to have an active CL (<15 mm) or a CL that decreased 10 mm or greater from Days 13 to 20, and to have a follicle of 12 mm or greater received GnRH and TAI on Day 21. Pregnancy diagnosis was performed on Day 32. Nonpregnant control cows (n = 102) were resynchronized immediately using Ovsynch-56, and control heifers (n = 76) were resynchronized using 5-day Cosynch starting on Day 34; therefore, cows and heifers were reinseminated on Day 42. Nonpregnant 21dRES animals that had not been reinseminated on Day 21 were resynchronized concurrently with the control animals. Pregnancy per AI (PAI) for the initial TAI was similar (P = 0.80) for 21dRES and control cows (30.3% vs. 29.4%) and heifers (49.4% vs. 51.3%). Of the nonpregnant 21dRES animals, 33 of 76 cows (43.4%) and 22 of 39 heifers (56.4%) had been reinseminated on Day 21. Therefore, the RI was decreased by 9.9 days (33.3 ± 1.0 vs. 43.2 ± 1.0 days; P < 0.001) in 21dRES cows and by 12.2 days in 21dRES heifers (30.1 ± 1.3 vs. 42.3 ± 1.3 days; P < 0.001) compared with controls. The overall resynchronized PAI was similar for 21dRES cows compared with controls (31.6% vs. 25.0%; P = 0.23). The PAI was 24.2% for 21dRES cows reinseminated on Day 21 and 37.2% for 21dRES cows reinseminated on Day 42. The overall resynchronized PAI was increased for 21dRES heifers compared with controls (57.5% vs. 32.4%; P = 0.03) because 21dRES heifers reinseminated on Day 21 had similar PAI compared with controls (43.5% vs. 32.4%; P = 0.39), but PAI was increased for 21dRES heifers reinseminated on Day 42 compared with controls (76.5% vs. 32.4%; P = 0.003). Consequently, the proportion of animals pregnant from the initial and resynchronized TAI tended to be increased in 21dRES heifers (79.0% vs. 67.1%; P = 0.09). Cost per pregnancy was decreased for the 21dRES in heifers. In conclusion, 21dRES provided a useful method to decrease the RI in cows and heifers, and to increase PAI and decrease cost per pregnancy in heifers.

Gendering gametes: The unequal contributions of sperm and egg donors.

This paper compares three groups of gestational mothers who relied on gametes from donors they did not know. The three groups are women who have conceived with donor sperm and their own eggs, women who have conceived with donor eggs and a partner's sperm, and women who have conceived with embryos composed of both donor eggs and donor sperm. The paper explores three issues. First, it considers whether intending parents select sperm and egg donors for different attributes both when they are chosen as the only donor and when they are chosen as donors contributing to an entire embryo. Second, it examines how women imagine the donor. Finally, it looks at how women conceptualize the donor as an individual who contributes to their child's characteristics. Two significant findings emerged in this analysis of survey data. First, the data show that gametes are gendered with different attributes both when those gametes are separate and even more so when seen as complementary parts of a whole. Second, the data show that women minimize the impact of the egg donor (both when a sole contribution and especially when part of the complementary whole) and thus ignore the influence or impact of the egg donor relative to how they make sense of the influence or impact of the sperm donor. The data for this study comes from an online survey developed by the authors.