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BMC Women's Health Oct 2023Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation... (Review)
Review
BACKGROUND
Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results.
AIMS
This review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines.
METHODS
The primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected.
DISCUSSION/CONCLUSION
This review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women < 38 years, with good prognosis, and IVF could be offered first to those > 38 years. Patients should be appropriately counselled to enable informed decision making.
Topics: Pregnancy; Female; Humans; Insemination, Artificial; Fertilization in Vitro; Infertility; Pregnancy Outcome; Pregnancy Rate; Ovulation Induction
PubMed: 37891606
DOI: 10.1186/s12905-023-02717-1 -
PloS One 2023Early pregnancy diagnosis is key to maximise productivity of dairy herds. We previously showed that an increase in the levels of miR-26 could be detected as soon as day...
Early pregnancy diagnosis is key to maximise productivity of dairy herds. We previously showed that an increase in the levels of miR-26 could be detected as soon as day 8 of pregnancy in heifers. The aims of this study were to determine whether 1) plasma miR-26 levels would be distinctly elevated, retrospectively, early after artificial insemination in lactating cows with successful compared to failed pregnancies, 2) the early increase in miRNA levels in cows with successful pregnancy could be accounted for by changes in miRNA expression in white blood cells (WBCs), presumably induced by the effects of embryo-derived interferon tau (IFNt), and 3) plasma miRNA levels may provide a reliable early predictor of pregnancy that could be used at a herd level. Blood samples were taken from a total of 34 dairy cows (lactation number 1 to 4) before (D0) and 9 and 18 days after artificial insemination at oestrus, followed by confirmation of pregnancy status by ultrasound on D32. In addition, WBCs collected from non-pregnant cows (n = 4) were stimulated in vitro with recombinant ovine IFNt (0-100 pg/ml). Levels of miRNAs and ISG15, a known IFNt-induced gene, were quantified by qPCR. Relative to D0, a larger increase in plasma miR-26a (P = 0.04) occurred on D9 in cows later confirmed to be pregnant (n = 12) than in cows with a failed pregnancy (n = 22). Expression of miR-26a in WBCs was not affected (P>0.1) by pregnancy status or IFNt stimulation in vitro, in contrast to ISG15 expression which increased markedly (P<0.0001) both in WBC samples collected on D18 from animals later confirmed to be pregnant, and in WBCs after stimulation with IFNt in vitro. Finally, ROC analyses revealed that miR-26a on D9 or D18 could predict pregnancy outcome with much lower accuracy than WBC ISG15 on D18 (Likelihood ratio, 2.3 vs 15.4). In summary, a modest increase in plasma miR-26a levels occurs during early pregnancy in mature dairy cows which may not accounted for by changes in miRNA levels in WBCs or the effects of IFNt. Moreover, compared to ISG15, changes in miR-26a levels may not provide an accurate test for early diagnosis of pregnancy in cows.
Topics: Pregnancy; Cattle; Animals; Female; Sheep; Pregnancy Outcome; Lactation; Retrospective Studies; Insemination, Artificial; MicroRNAs; Progesterone
PubMed: 37566616
DOI: 10.1371/journal.pone.0289342 -
JAMA Network Open May 2024Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their...
IMPORTANCE
Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations.
OBJECTIVE
To assess the risk of cancer, overall and by cancer type, among children born after MAR compared with children conceived naturally.
DESIGN, SETTING, AND PARTICIPANTS
For this cohort study, the French National Mother-Child Register (EPI-MERES) was searched for all live births that occurred in France between January 1, 2010, and December 31, 2021 (and followed up until June 30, 2022). The EPI-MERES was built from comprehensive data of the French National Health Data System. Data analysis was performed from December 1, 2021, to June 30, 2023.
EXPOSURE
Use of assisted reproduction technologies (ART), such as fresh embryo transfer (ET) or frozen ET (FET), and artificial insemination (AI).
MAIN OUTCOMES AND MEASURES
The risk of cancer was compared, overall and by cancer type, among children born after fresh ET, FET, or AI and children conceived naturally, using Cox proportional hazards regression models adjusted for maternal and child characteristics at birth.
RESULTS
This study included 8 526 306 children with a mean (SD) age of 6.4 (3.4) years; 51.2% were boys, 96.4% were singletons, 12.1% were small for gestational age at birth, and 3.1% had a congenital malformation. There were 260 236 children (3.1%) born after MAR, including 133 965 (1.6%) after fresh ET, 66 165 (0.8%) after FET, and 60 106 (0.7%) after AI. A total of 9256 case patients with cancer were identified over a median follow-up of 6.7 (IQR, 3.7-9.6) years; 165, 57, and 70 were born after fresh ET, FET, and AI, respectively. The overall risk of cancer did not differ between children conceived naturally and those born after fresh ET (hazard ratio [HR], 1.12 [95% CI, 0.96 to 1.31]), FET (HR, 1.02 [95% CI, 0.78 to 1.32]), or AI (HR, 1.09 [95% CI, 0.86 to 1.38]). However, the risk of acute lymphoblastic leukemia was higher among children born after FET (20 case patients; HR 1.61 [95% CI, 1.04 to 2.50]; risk difference [RD], 23.2 [95% CI, 1.5 to 57.0] per million person-years) compared with children conceived naturally. Moreover, among children born between 2010 and 2015, the risk of leukemia was higher among children born after fresh ET (45 case patients; HR, 1.42 [95% CI, 1.06 to 1.92]; adjusted RD, 19.7 [95% CI, 2.8 to 43.2] per million person-years).
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that children born after FET or fresh ET had an increased risk of leukemia compared with children conceived naturally. This risk, although resulting in a limited number of cases, needs to be monitored in view of the continuous increase in the use of ART.
Topics: Humans; Female; Neoplasms; Reproductive Techniques, Assisted; Male; Child; France; Child, Preschool; Risk Factors; Adult; Pregnancy; Cohort Studies; Registries; Proportional Hazards Models; Infant; Embryo Transfer
PubMed: 38696167
DOI: 10.1001/jamanetworkopen.2024.9429 -
Microbiology Spectrum Dec 2023Emerging evidence suggests that microbiome-targeted approaches may provide a novel opportunity to reduce the incidence of reproductive failures in cattle. To develop...
Sequencing and culture-based characterization of the vaginal and uterine microbiota in beef cattle that became pregnant or remained open following artificial insemination.
Emerging evidence suggests that microbiome-targeted approaches may provide a novel opportunity to reduce the incidence of reproductive failures in cattle. To develop such microbiome-based strategies, one of the first logical steps is to identify reproductive microbiome features related to fertility and to isolate the fertility-associated microbial species for developing a future bacterial consortium that could be administered before breeding to enhance pregnancy outcomes. Here, we characterized the vaginal and uterine microbiota in beef cattle that became pregnant or remained open via artificial insemination and identified microbiota features associated with fertility. We compared similarities between vaginal and uterine microbiota and between heifers and cows. Using culturing, we provided new insights into the culturable fraction of the vaginal and uterine microbiota and their antimicrobial resistance. Overall, our findings will serve as an important basis for future research aimed at harnessing the vaginal and uterine microbiome for improved cattle fertility.
Topics: Pregnancy; Cattle; Animals; Female; Reproduction; Vagina; Insemination, Artificial; Fertility; Microbiota
PubMed: 37921486
DOI: 10.1128/spectrum.02732-23 -
Theriogenology Oct 2023The individual resistance or tolerance against uterine disease in dairy cattle might be related to variations in the uterine tract microbiota. The uterine tract...
The individual resistance or tolerance against uterine disease in dairy cattle might be related to variations in the uterine tract microbiota. The uterine tract microbiota in dairy cattle is a field of increasing interest. However, its specific taxonomy and functional aspects is under-explored, and information about the microbiota in the endometrium at artificial insemination (AI) is still missing. Although uterine bacteria are likely to be introduced via the vaginal route, it has also been suggested that pathogens can be transferred to the uterus via a hematogenous route. Thus, the microbiota in different layers of the uterine wall may differ. Norwegian Red (NR) is a high fertility breed that also has a high prevalence of subclinical endometritis (SCE), an inflammation of the uterus that has a negative effect on dairy cattle fertility. However, in this breed the negative effect is only moderate, raising the question of whether this may be due to a favorable microbiota. In the present study we investigated the endometrial microbiota in NR at AI by biopsy and cytobrush samples, and comparing this to the vaginal microflora. The second objective was to describe potential differences at both distinct depths of the endometrium, in healthy vs SCE positive NR cows. We sampled 24 lactating and clinically healthy Norwegian red cows in their second heat or more after calving, presented for first AI. First, we obtained a vaginal swab and a cytobrush sample, in addition to a cytotape to investigate the animal's uterine health status with respect to SCE. Secondly, we acquired a biopsy sample from the uterine endometrium. Bacterial DNA from the 16S rRNA gene was extracted and sequenced with Illumina sequencing of the V3-V4 region. Alpha and beta diversity and taxonomic composition was investigated. Our results showed that the microbiota of endometrial biopsies was qualitatively different and more even than that of cytobrush and vaginal swab samples. The cytobrush samples and the vaginal swabs shared a similar taxonomic composition, suggesting that vaginal swabs may suffice to sample the surface-layer uterine microbiota at estrus. The current study gave a description of the microbiota in the healthy and SCE positive NR cows at AI. Our results are valuable as we continue to explore the mechanisms for high fertility in NR, and possible further improvements.
Topics: Female; Cattle; Animals; Lactation; RNA, Ribosomal, 16S; Endometritis; Insemination, Artificial; Biopsy; Microbiota; Cattle Diseases
PubMed: 37390751
DOI: 10.1016/j.theriogenology.2023.06.024 -
Theriogenology Dec 2023Despite being the most important form of biotechnology in animal reproduction, artificial insemination was used in about 23% of Brazilian bovine herds in 2021. This is...
Despite being the most important form of biotechnology in animal reproduction, artificial insemination was used in about 23% of Brazilian bovine herds in 2021. This is due to the variability of results caused by varying bull fertility and body condition of the cows. This study aimed to correlate the fertility indices of bulls with qualitative attributes of the semen. Semen samples from 28 bulls (Nellore and Angus) were used to evaluate postthaw sperm morphology and kinetics using conventional analysis, image-based flow cytometry (IBFC) and computer-assisted semen analysis (CASA). The fertility index was effective in separating bulls into 4 different fertility classes (P < 0.001), and fertility rates in timed artificial insemination (TAI) remained constant between the cows' fertility categories (P < 0.001) and in the different grades of female body condition (P < 0.005). After partial least squares regression (PLS) analysis, four models were proposed with different variables. The coefficients of determination for the conventional analysis, CASA, and IBCFC models were 0.154, 0.380, and 0.259, respectively. The composite model, including select IBFC and CASA parameters, showed a greater R (0.481) with progressive motility, average speed (VAP, μm/s), membrane integrity, and mitochondrial potential, showing a positive effect. Linear speed (VSL, μm/s) and acrosomal integrity had a negative effect on bull fertility indices. Bulls classified by the fertility index attained dispersed pregnancy rates in different cow body condition score (BCS) classes, and the sperm quality pattern was consistent with this classification. In conclusion, this novel composite model including CASA and IBFC parameters improves the prediction of bull fertility used in TAI.
PubMed: 37722295
DOI: 10.1016/j.theriogenology.2023.09.001 -
Animal Reproduction 2023The aim of the present study was to evaluate semen cryopreservation with ACP-Lact® diluent, which consists of coconut water powder (ACP) added to goat milk powder....
The aim of the present study was to evaluate semen cryopreservation with ACP-Lact® diluent, which consists of coconut water powder (ACP) added to goat milk powder. After thawing, the samples were evaluated for sperm kinetics, membrane evaluation and insemination. For cryopreservation, a pool was made with the ejaculate of six goats, diluted in four equal aliquots for the respective treatments: T1 (ACP-Lact®); T2 (ACP-Lact® 50%); T3 (ACP + 2.5% egg yolk) and T4 (Tris + 2.5% egg yolk). After dilution of the treatments, the samples were placed in 0.5 ml straws and chilled at a rate of -1.07°C/min. After reaching 4°C and stabilizing for one hour, the straws were placed in nitrogen vapour at -60°C for 15 minutes and then immersed in liquid nitrogen (-196ºC). The straws were thawed in a 37°C water bath and kinetic assessments were performed immediately using a computerized semen analysis program (CSA), viability (EN), membrane functionality (HOST), mitochondrial activity (DAB) and DNA integrity assessment of spermatozoa. For the experiment, ten goats were inseminated, divided into two groups of five goats each, G1 inseminated with ACP-Lact® and G2 with ACP, by fixed-time artificial insemination (FTAI). Regarding the kinetic parameters, the ACP-Lact® treatment showed higher progressive motility (PM) and sperm velocity than the other treatments (36.77%). In the VSL parameter the ACP-Lact diluent was superior to ACP and Tris. In viability the treatment with ACP-Lact® was superior to the treatment with Tris, 95% and 83% respectively. In FTAI two goats were born out of the 5 goats inseminated with ACP-Lact®. It was concluded that the use of ACP-Lact® for cryopreservation of caprine semen is efficient in maintaining seminal parameters during thawing in vitro and in vivo and proved to be a good alternative extender for the caprine species.
PubMed: 38025996
DOI: 10.1590/1984-3143-AR2023-0081 -
The Journal of Reproduction and... Feb 2024This study investigated the effects of timed artificial insemination (TAI) and equine chorionic gonadotropin (eCG) administration on lactating dairy cows under...
This study investigated the effects of timed artificial insemination (TAI) and equine chorionic gonadotropin (eCG) administration on lactating dairy cows under heat-stress conditions (average temperature-humidity index: 80). Timed artificial insemination was performed on the cows with (n = 57) or without (control, n = 41) supplementation with 500 IU of eCG at the day of PGF treatment using the CIDR-Ovsynch protocol. GnRH was administered, and a progesterone device (CIDR) was inserted on Day -10 of the treatment protocol. The CIDR was removed on Day -3, and the cows were treated with PGF. Two days later, a 2 GnRH injection was administered. Subsequently, AI was performed on Day 0 (16-20 h after the 2 GnRH injection), and pregnancy was diagnosed on Days 32 and 60. Plasma progesterone (P) concentrations were measured after AI. Results showed that the eCG group had a higher pregnancy per AI (P/AI) than the control group (43.9 vs. 12.2%, P = 0.002), which was also accompanied by elevated P levels. Four cows in the eCG group had multiple calves, representing 7.0 and 16.0% of the group and pregnant cows, respectively. In conclusion, 500 IU of eCG combined with CIDR-Ovsynch in lactating dairy cows under severe heat stress conditions successfully improved fertility. However, the protocol may have a slight risk of multiple births.
Topics: Pregnancy; Female; Cattle; Animals; Horses; Progesterone; Lactation; Dinoprost; Gonadotropin-Releasing Hormone; Estrus Synchronization; Insemination, Artificial; Chorionic Gonadotropin
PubMed: 38171736
DOI: 10.1262/jrd.2023-069 -
Journal of Dairy Science Dec 2023This study aimed to determine whether 200 μg of GnRH (gonadorelin hydrochloride) would increase ovulatory response and pregnancies per artificial insemination (P/AI)...
Effect of using 200 μg of gonadorelin at the first gonadotropin-releasing hormone of the breeding-Ovsynch on ovulatory response and pregnancies per artificial insemination in first-service lactating Holstein cows.
This study aimed to determine whether 200 μg of GnRH (gonadorelin hydrochloride) would increase ovulatory response and pregnancies per artificial insemination (P/AI) compared with 100 μg at the first GnRH of the breeding-Ovsynch of a Double-Ovsynch program (DO) in lactating Holstein cows. Weekly cohorts of primiparous (n = 719) and multiparous (n = 1,191) cows submitted to DO (GnRH, 7 d later PGF, 3 d later GnRH, 7 d later GnRH [G1], 7 d later PGF [PG1], 1 d later PGF, ∼32 h later GnRH [G2], and ∼16 h later timed artificial insemination [TAI]) for first service, randomly received either 100 μg or 200 μg of GnRH (gonadorelin hydrochloride) at G1 (primiparous, 64-75 DIM; multiparous, 59-70 DIM). Ovulation was determined by ultrasound 2 d after G1 (n = 1,294) and 2 d after G2 (n = 1,020). Blood samples were collected at G1 and at PG1 d to evaluate serum progesterone (P4) concentrations. Conventional (n = 314, Angus; n = 1,084, Holstein) and Holstein sexed semen (n = 276) were used. Pregnancy was diagnosed on d 32, 46, 88, and 200 post-TAI. The high dose of GnRH (200 μg) increased overall ovulatory response to G1 compared with 100 μg (81.3% vs. 65.1%), being similar between parities (primiparous, 72.2%; multiparous, 73.9%). Mean serum P4 concentrations at PG1 did not differ between treatments (100 µg: 9.59 ± 0.15 ng/mL vs. 200 µg: 9.43 ± 0.15 ng/mL). Cows with no ovulation to G1 had higher serum P4 concentrations at G1 than cows with ovulation to G1 (6.27 ± 0.19 ng/mL vs. 4.66 ± 0.07 ng/mL). At PG1, the proportion of cows with functional corpus luteum (98.7% vs. 89.7%) and serum P4 concentrations (9.68 ± 0.12 ng/mL vs. 9.14 ± 0.22 ng/mL) were greater in cows that ovulated to G1 compared with cows that did not ovulate. Also, cows that ovulated to G1 had a greater increase in serum P4 concentrations from G1 to PG1 than cows with no ovulation (5.26 ± 0.12 ng/mL vs. 3.32 ± 0.25 ng/mL). The high dose of GnRH improved overall P/AI at 32 d post-TAI in cows inseminated with conventional semen (54.6% vs. 48.2%) and tended to improve P/AI on 46 (48.8% vs. 44.9%), 88 (47.6% vs. 43.4%), and 200 (45.3% vs. 41.2%) d post-TAI. Primiparous cows inseminated with conventional semen had better P/AI than multiparous cows at d 32 (58.2% vs. 49.4%), 46 (55.1% vs. 44.4%), 88 (53.2% vs. 43.2%) and 200 (51.6% vs. 40.7%) post-TAI. Primiparous cows treated with 200 µg GnRH had lower P/AI on d 32, 46, 88, and 200 post-TAI when inseminated with sexed semen than with conventional semen. In summary, the higher dose of GnRH at G1 improved ovulatory response and P/AI at d 32 post-TAI and tended to improve P/AI at d 46, 88, and 200 post-TAI in cows inseminated with conventional semen. Moreover, the effect of treatment on P/AI in primiparous cows depended on semen type (conventional vs. sexed semen).
Topics: Pregnancy; Female; Cattle; Animals; Progesterone; Lactation; Estrus Synchronization; Dinoprost; Ovulation; Insemination, Artificial; Gonadotropin-Releasing Hormone; Fertility
PubMed: 37641336
DOI: 10.3168/jds.2023-23416 -
Andrology Dec 2023Obtaining functional sperm cells is the first step to treat infertility. With the ever-increasing trend in male infertility, clinicians require access to effective... (Review)
Review
BACKGROUND
Obtaining functional sperm cells is the first step to treat infertility. With the ever-increasing trend in male infertility, clinicians require access to effective solutions that are able to single out the most viable spermatozoa, which would max out the chance for a successful pregnancy. The new generation techniques for sperm selection involve microfluidics, which offers laminar flow and low Reynolds number within the platforms can provide unprecedented opportunities for sperm selection. Previous studies showed that microfluidic platforms can provide a novel approach to this challenge and since then researchers across the globe have attacked this problem from multiple angles.
OBJECTIVE
In this review, we seek to provide a much-needed bridge between the technical and medical aspects of microfluidic sperm selection. Here, we provide an up-to-date list on microfluidic sperm selection procedures and its application in assisted reproductive technology laboratories.
SEARCH METHOD
A literature search was performed in Web of Science, PubMed, and Scopus to select papers reporting microfluidic sperm selection using the keywords: microfluidic sperm selection, self-motility, non-motile sperm selection, boundary following, rheotaxis, chemotaxis, and thermotaxis. Papers published before March 31, 2023 were selected.
OUTCOMES
Our results show that most studies have used motility-based properties for sperm selection. However, microfluidic platforms are ripe for making use of other properties such as chemotaxis and especially rheotaxis. We have identified that low throughput is one of the major hurdles to current microfluidic sperm selection chips, which can be solved via parallelization.
CONCLUSION
Future work needs to be performed on numerical simulation of the microfluidics chip prior to fabrication as well as relevant clinical assessment after the selection procedure. This would require a close collaboration and understanding among engineers, biologists, and medical professionals. It is interesting that in spite of two decades of microfluidics sperm selection, numerical simulation and clinical studies are lagging behind. It is expected that microfluidic sperm selection platforms will play a major role in the development of fully integrated start-to-finish assisted reproductive technology systems.
PubMed: 38148634
DOI: 10.1111/andr.13578