Timed-AI after synchronization of ovulation has become one of the most used reproductive technologies developed during the past 40 years. Various adaptations of this technology are now extensively ...used worldwide, in the beef and dairy cattle industry. Our well-cited report, published in Theriogenology in 1995, presented a method termed Ovsynch, that used GnRH and PGF2α to perform synchronization of ovulation and timed AI in lactating dairy cows. This report introduced Ovsynch, more as a concept of induced ovulation, and demonstrated the ovarian dynamics during the protocol. Validation and improvements on this method were subsequently performed in numerous university studies and on commercial dairies, worldwide. This review will provide a brief historical background, some personal recollections, and certain modifications that have been made in synchronization of ovulation protocols. Each section emphasizes the physiology that underlies the most widely-used synchronization of ovulation protocols and key modifications and some practical application of these protocols on commercial operations. Finally, the effect of timed AI in the US dairy industry and in the Brazilian beef cattle industry are compared. Although numerous studies have been done using these protocols, there is still substantial need for research to improve the synchronization, efficacy, simplicity, and practical application of these protocols.
Management of the ovine oestrous cycle is mainly based on the use of exogenous hormones to mimic or enhance (progesterone and its analogues) or manipulate (prostaglandin F2α and its analogues) the ...activity of the corpus luteum, combined with the application of other hormones mimicking the pituitary secretion of gonadotrophins (e.g. equine chorionic gonadotrophin). These protocols have been applied without major change for decades but, now, there are two reasons to reconsider them: (1) our greatly improved knowledge of the dynamics of ovarian physiology, following the application of transrectal ultrasonography, indicates that modification of the protocols may improve fertility yields and (2) increasing concerns about animal health and welfare, food safety and the environmental impact of the treatments, as evidenced by public opinion and therefore market forces. Here, we offer an overview of these issues, introduce an updated protocol and suggest ways for future improvements to the protocols.
Intra-uterine insemination (IUI) is a widely-used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), ...the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rates.
To determine whether, for couples with unexplained subfertility, the live birth rate is improved following IUI treatment with or without OH compared to timed intercourse (TI) or expectant management with or without OH, or following IUI treatment with OH compared to IUI in a natural cycle.
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 17 October 2019, together with reference checking and contact with study authors for missing or unpublished data.
Randomised controlled trials (RCTs) comparing IUI with TI or expectant management, both in stimulated or natural cycles, or IUI in stimulated cycles with IUI in natural cycles in couples with unexplained subfertility.
Two review authors independently performed study selection, quality assessment and data extraction. Primary review outcomes were live birth rate and multiple pregnancy rate.
We include 15 trials with 2068 women. The evidence was of very low to moderate quality. The main limitation was very serious imprecision. IUI in a natural cycle versus timed intercourse or expectant management in a natural cycle It is uncertain whether treatment with IUI in a natural cycle improves live birth rate compared to treatment with expectant management in a natural cycle (odds ratio (OR) 1.60, 95% confidence interval (CI) 0.92 to 2.78; 1 RCT, 334 women; low-quality evidence). If we assume the chance of a live birth with expectant management in a natural cycle to be 16%, that of IUI in a natural cycle would be between 15% and 34%. It is uncertain whether treatment with IUI in a natural cycle reduces multiple pregnancy rates compared to control (OR 0.50, 95% CI 0.04 to 5.53; 1 RCT, 334 women; low-quality evidence). IUI in a stimulated cycle versus timed intercourse or expectant management in a stimulated cycle It is uncertain whether treatment with IUI in a stimulated cycle improves live birth rates compared to treatment with TI in a stimulated cycle (OR 1.59, 95% CI 0.88 to 2.88; 2 RCTs, 208 women; I
= 72%; low-quality evidence). If we assume the chance of achieving a live birth with TI in a stimulated cycle was 26%, the chance with IUI in a stimulated cycle would be between 23% and 50%. It is uncertain whether treatment with IUI in a stimulated cycle reduces multiple pregnancy rates compared to control (OR 1.46, 95% CI 0.55 to 3.87; 4 RCTs, 316 women; I
= 0%; low-quality evidence). IUI in a stimulated cycle versus timed intercourse or expectant management in a natural cycle In couples with a low prediction score of natural conception, treatment with IUI combined with clomiphene citrate or letrozole probably results in a higher live birth rate compared to treatment with expectant management in a natural cycle (OR 4.48, 95% CI 2.00 to 10.01; 1 RCT; 201 women; moderate-quality evidence). If we assume the chance of a live birth with expectant management in a natural cycle was 9%, the chance of a live birth with IUI in a stimulated cycle would be between 17% and 50%. It is uncertain whether treatment with IUI in a stimulated cycle results in a lower multiple pregnancy rate compared to control (OR 3.01, 95% CI 0.47 to 19.28; 2 RCTs, 454 women; I
= 0%; low-quality evidence). IUI in a natural cycle versus timed intercourse or expectant management in a stimulated cycle Treatment with IUI in a natural cycle probably results in a higher cumulative live birth rate compared to treatment with expectant management in a stimulated cycle (OR 1.95, 95% CI 1.10 to 3.44; 1 RCT, 342 women: moderate-quality evidence). If we assume the chance of a live birth with expectant management in a stimulated cycle was 13%, the chance of a live birth with IUI in a natural cycle would be between 14% and 34%. It is uncertain whether treatment with IUI in a natural cycle results in a lower multiple pregnancy rate compared to control (OR 1.05, 95% CI 0.07 to 16.90; 1 RCT, 342 women; low-quality evidence). IUI in a stimulated cycle versus IUI in a natural cycle Treatment with IUI in a stimulated cycle may result in a higher cumulative live birth rate compared to treatment with IUI in a natural cycle (OR 2.07, 95% CI 1.22 to 3.50; 4 RCTs, 396 women; I
= 0%; low-quality evidence). If we assume the chance of a live birth with IUI in a natural cycle was 14%, the chance of a live birth with IUI in a stimulated cycle would be between 17% and 36%. It is uncertain whether treatment with IUI in a stimulated cycle results in a higher multiple pregnancy rate compared to control (OR 3.00, 95% CI 0.11 to 78.27; 2 RCTs, 65 women; low-quality evidence).
Due to insufficient data, it is uncertain whether treatment with IUI with or without OH compared to timed intercourse or expectant management with or without OH improves cumulative live birth rates with acceptable multiple pregnancy rates in couples with unexplained subfertility. However, treatment with IUI with OH probably results in a higher cumulative live birth rate compared to expectant management without OH in couples with a low prediction score of natural conception. Similarly, treatment with IUI in a natural cycle probably results in a higher cumulative live birth rate compared to treatment with timed intercourse with OH. Treatment with IUI in a stimulated cycle may result in a higher cumulative live birth rate compared to treatment with IUI in a natural cycle.
An experiment was conducted to compare the 7 & 7 Synch and 7-day CO-Synch + controlled internal drug release (CIDR®) treatment regimens before fixed-time artificial insemination (FTAI) of beef cows ...with conventional or sex-sorted semen. Cows (n = 1538) were blocked based on age and days postpartum (DPP) and randomly assigned to treatment regimen and semen type. Cows assigned to the 7-day CO-Synch + CIDR treatment regimen (n = 769) were administered gonadotropin-releasing hormone (GnRH) and an intravaginal progesterone-releasing insert (CIDR) on Day − 10, and administration of prostaglandin F2α (PG) coincident with CIDR removal on Day − 3. Cows assigned to 7 & 7 Synch (n = 769) were administered PG and a CIDR device on Day − 17, GnRH on Day − 10, and PG coincident with CIDR removal on Day − 3. Cows were administered GnRH coincident with FTAI, which was performed 66 h after CIDR removal with conventional (20 × 106 cells) or sex-sorted (4 × 106 cells) semen. Expression of estrus was affected by treatment regimen (P = 0.01) and by treatment regimen × DPP (P = 0.0004), as a result of imposing the 7 & 7 Synch regimen; therefore, a greater percentage of cows expressed estrus (82% compared with 64%), particularly among cows with greater DPP. Pregnancy percentages resulting from FTAI were less (P < 0.0001) when using sex-sorted semen but greater among cows treated with 7 & 7 Synch (conventional semen: 72%; sex-sorted semen: 52%) compared with 7-day CO-Synch + CIDR (conventional semen: 61%; sex-sorted semen: 44%).
•7 & 7 Synch and 7-day CO-Synch + CIDR were compared among postpartum beef cows.•7 & 7 Synch resulted in greater expression of estrus and pregnancy rates to AI.•Improved pregnancy results were observed with conventional and sex-sorted semen.•Interactions observed suggest 7 & 7 Synch is most effective among cyclic cows.
ObjectiveTo compare success rates, associated risks and cost-effectiveness between intrauterine insemination (IUI) and in vitro fertilisation (IVF).DesignRetrospective observational study.SettingThe ...UK from 2012 to 2016.ParticipantsData from Human Fertilisation and Embryology Authority’s freedom of information request for 2012–2016 for IVF/ICSI (intracytoplasmic sperm injection)and IUI as practiced in 319 105 IVF/ICSI and 30 669 IUI cycles. Direct-cost calculations for maternal and neonatal expenditure per live birth (LB) was constructed using the cost of multiple birth model, with inflation-adjusted Bank of England index-linked data. A second direct-cost analysis evaluating the incremental cost-effective ratio (ICER) was modelled using the 2016 national mean (baseline) IVF and IUI success rates.Outcome measuresLB, risks from IVF and IUI, and costs to gain 1 LB.ResultsThis largest comprehensive analysis integrating success, risks and costs at a national level shows IUI is safer and more cost-effective than IVF treatment.IVF LB/cycle success was significantly better than IUI at 26.96% versus 11.49% (p<0.001) but the IUI success is much closer to IVF at 2.35:1, than previously considered. IVF remains a significant source of multiple gestation pregnancy (MGP) compared with IUI (RR (Relative Risk): 1.45 (1.31 to 1.60), p<0.001) as was the rate of twins (RR: 1.58, p<0.001).In 2016, IVF maternal and neonatal cost was £115 082 017 compared with £2 940 196 for IUI and this MGP-related perinatal cost is absorbed by the National Health Services. At baseline tariffs and success rates IUI was £42 558 cheaper than IVF to deliver 1LB with enhanced benefits with small improvements in IUI. Reliable levels of IVF-related MGP, OHSS (ovarian hyperstimulation syndrome), fetal reductions and terminations are revealed.ConclusionIUI success rates are much closer to IVF than previously reported, more cost-effective in delivering 1 LB, and associated with lower risk of complications for maternal and neonatal complications. It is prudent to offer IUI before IVF nationally.
Heat stress has consequences on both the physiology and reproductive performance of cows, but the most dramatic effect for dairy producers is the decrease produced in fertility. The effects of heat ...stress on fertility include an increased number of days open, reduced conception rate, and larger number of cows suffering different types of anestrus. Once becomes pregnant, heat stress affects also the reproductive success of the cow through its direct effects on the ovary, uterus, gametes, embryo, and early fetus. This article reviews current knowledge of the effects of heat stress on fertility in dairy cows and the hormonal strategies used to mitigate these effects at the farm level. Administration of GnRH at the moment of artificial insemination can improve the conception rate. Breeding synchronization protocols for fixed-time insemination may reduce the calving conception interval and the number of services per conception. Progesterone-based protocols seem resolve better the reproductive disorders related to a hot environment (anestrus) than GnRH-based protocols. The use of combinations of GnRH, eCG, and hCG in progesterone-based protocols can improve results. Progesterone supplementation during the late embryonic and/or early fetal period would be useful in curtailing pregnancy losses, mainly in single pregnancies, whereas a more positive effect of treatment with GnRH than progesterone has been found in twin pregnancies. Melatonin therapy is emerging as a promising strategy to improve the natural reproductive performance of cows suffering conditions of heat stress.
Our objective was to compare the AI submission rate and pregnancies per artificial insemination (P/AI) at first service of lactating Holstein cows submitted to a Double-Ovsynch protocol and timed ...artificial insemination (TAI) versus artificial insemination (AI) to a detected estrus after synchronization of estrus at a similar day in milk range. Lactating Holstein cows were randomly assigned to receive their first TAI after a Double-Ovsynch protocol (DO; n = 294) or to receive their first AI after a synchronized estrus (EST; n = 284). Pregnancy status was determined 33 ± 3 d after insemination and was reconfirmed 63 ± 3 d after insemination. Data were analyzed by ANOVA and logistic regression using the MIXED and GLIMMIX procedures of SAS (SAS Institute Inc., Cary, NC). By design, days in milk at first insemination did not differ between treatments (76.9 ± 0.2 vs. 76.7 ± 0.3 for DO vs. EST cows, respectively), but more DO cows were inseminated within 7 d after the end of the voluntary waiting period than EST cows (100.0 vs. 77.5%). Overall, DO cows had more P/AI than EST cows at both 33 d (49.0 vs. 38.6%) and 63 d (44.6 vs. 36.4%) after insemination, but pregnancy loss from 33 to 63 d after insemination did not differ between treatments. Primiparous cows had more P/AI than multiparous cows 33 and 63 d after insemination, but the treatment by parity interaction was not significant. Synchronization rate to the hormonal protocols was 85.3%, which did not differ between treatments; however, synchronized DO cows had more P/AI 33 d after insemination than synchronized EST cows (54.7 vs. 44.5%). In summary, submission of lactating Holstein cows to a Double-Ovsynch protocol and TAI for first insemination increased the percentage of cows inseminated within 7 d after the end of the voluntary waiting period and increased P/AI at 33 and 63 d after first insemination resulting in 64 and 58% more pregnant cows, respectively, than submission of cows for first AI after detection of estrus at a similar day in milk range. We conclude that, because the proportion of synchronized cows did not differ between treatments, DO cows had more P/AI than EST cows because of an intrinsic increase in fertility after submission to a fertility program.
While sperm cryopreservation is the best technology to store boar semen for long‐term periods, only 1% of all artificial inseminations (AI) conducted worldwide are made using frozen–thawed boar ...sperm. With the emergence of long‐term extenders for liquid storage, the use of cryopreserved sperm in routine AI is less required. However, banks of boar semen contain cryopreserved sperm and planning inseminations in AI centres may benefit from the use of frozen–thawed semen. Therefore, there is an interest in the use of this technology to preserve boar sperm. In this regard, although the first attempts to cryopreserve boar semen date back to the seventies and this technology is still considered as optimal, some relevant improvements have been made in the last decade. After giving a general picture about boar sperm cryodamage, the present review seeks to shed light on these recent cryopreservation advances. These contributions regard to protein markers for predicting ejaculate freezability, sperm selection prior to start cryopreservation procedures, additives to freezing and thawing extenders, relevance of the AI‐technique and insemination‐to‐ovulation interval. In conclusion, most of these progresses have allowed counteracting better boar sperm cryodamage and are thus considered as forward steps for this storage method. It is also worth noting that, despite being lower than fresh/extended semen, reproductive performance outcomes following AI with frozen‐thawed boar sperm are currently acceptable.
The objective of this study was to compare circulating progesterone (P4) profiles and pregnancies per AI (P/AI) in lactating dairy cows bred by timed artificial insemination (TAI) following ...Ovsynch-56 after 2 different presynchronization protocols: Double-Ovsynch (DO) or Presynch-Ovsynch (PS). Our main hypothesis was that DO would increase fertility in primiparous cows, but not in multiparous cows. Within each herd (n=3), lactating dairy cows (n=1,687; 778 primiparous, 909 multiparous) were randomly assigned to DO n=837; GnRH-7d-PGF2α-3d-GnRH-7d-Ovsynch-56 (GnRH-7d-PGF2α-56h-GnRH-16hTAI) or PS (n=850; PGF2α-14d-PGF2α-12d-Ovsynch-56). In 1 herd, concentrations of P4 were determined at the first GnRH (GnRH1) of Ovsynch-56 and at d 11 after TAI (n=739). In all herds, pregnancy was diagnosed by palpation per rectum at 39 d. In 1 herd, the incidence of late embryo loss was determined at 74d, and data were available on P/AI at the subsequent second service. Presynchronization with DO reduced the percentage of animals with low P4 concentrations (<0.50ng/mL) at GnRH1 of Ovsynch-56 (5.4 vs. 25.3%, DO vs. PS). A lesser percentage of both primiparous and multiparous cows treated with DO had low P4 concentrations at GnRH1 of Ovsynch-56 (3.3 vs. 19.7%, DO vs. PS primiparous; and 8.8 vs. 31.9%, DO vs. PS multiparous). Presynchronization with DO improved P/AI at the first postpartum service (46.3 vs. 38.2%, DO vs. PS). Statistically, a fertility improvement could be detected for primiparous cows treated with DO (52.5 vs. 42.3%, DO vs. PS, primiparous), but only a tendency could be detected in multiparous cows (40.3 vs. 34.3%, DO vs. PS, multiparous), consistent with our original hypothesis. Presynchronization treatment had no effect on the incidence of late embryo loss after first service (8.5 vs. 5.5%, DO vs. PS). A lower body condition score increased the percentage of cows with low P4 at GnRH1 of Ovsynch-56 and reduced fertility to the TAI. In addition, P4 concentration at d 11 after TAI was reduced by DO. The method of presynchronization at first service had no effect on P/AI at the subsequent second service (34.7 vs. 36.5%, DO vs. PS). Thus, presynchronization with DO induced cyclicity in most anovular cows and improved fertility compared with PS, suggesting that DO could be a useful reproductive management protocol for synchronizing first service in commercial dairy herds.
STUDY QUESTION
The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during ...2009: are there any changes in the trends compared with previous years?
SUMMARY ANSWER
Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined.
WHAT IS KNOWN ALREADY
Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction.
STUDY DESIGN, SIZE, DURATION
Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis.
PARTICIPANTS/MATERIALS SETTING, METHODS
From 34 countries (−2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported.
MAIN RESULTS AND THE ROLE OF CHANCE
In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively.
LIMITATIONS, REASONS FOR CAUTION
The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution.
WIDER IMPLICATIONS OF THE FINDINGS
The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.
STUDY FUNDING/COMPETING INTERESTS
The study has no external funding; all costs are covered by ESHRE. There are no competing interests.
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