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The Cochrane Database of Systematic... Nov 2021Intrauterine insemination (IUI), combined with ovarian stimulation (OS), has been demonstrated to be an effective treatment for infertile couples. Several agents for... (Review)
Review
BACKGROUND
Intrauterine insemination (IUI), combined with ovarian stimulation (OS), has been demonstrated to be an effective treatment for infertile couples. Several agents for ovarian stimulation, combined with IUI, have been proposed, but it is still not clear which agents for stimulation are the most effective. This is an update of the review, first published in 2007.
OBJECTIVES
To assess the effects of agents for ovarian stimulation for intrauterine insemination in infertile ovulatory women.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trial registers from their inception to November 2020. We performed reference checking and contacted study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included truly randomised controlled trials (RCTs) that compared different agents for ovarian stimulation combined with IUI for infertile ovulatory women concerning couples with unexplained infertility. mild male factor infertility and minimal to mild endometriosis.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by Cochrane.
MAIN RESULTS
In this updated review, we have included a total of 82 studies, involving 12,614 women. Due to the multitude of comparisons between different agents for ovarian stimulation, we highlight the seven most often reported here. Gonadotropins versus anti-oestrogens (13 studies) For live birth, the results of five studies were pooled and showed a probable improvement in the cumulative live birth rate for gonadotropins compared to anti-oestrogens (odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05 to 1.79; I = 30%; 5 studies, 1924 participants; moderate-certainty evidence). This suggests that if the chance of live birth following anti-oestrogens is assumed to be 22.8%, the chance following gonadotropins would be between 23.7% and 34.6%. The pooled effect of seven studies revealed that we are uncertain whether gonadotropins lead to a higher multiple pregnancy rate compared with anti-oestrogens (OR 1.58, 95% CI 0.60 to 4.17; I = 58%; 7 studies, 2139 participants; low-certainty evidence). Aromatase inhibitors versus anti-oestrogens (8 studies) One study reported live birth rates for this comparison. We are uncertain whether aromatase inhibitors improve live birth rate compared with anti-oestrogens (OR 0.75, CI 95% 0.51 to 1.11; 1 study, 599 participants; low-certainty evidence). This suggests that if the chance of live birth following anti-oestrogens is 23.4%, the chance following aromatase inhibitors would be between 13.5% and 25.3%. The results of pooling four studies revealed that we are uncertain whether aromatase inhibitors compared with anti-oestrogens lead to a higher multiple pregnancy rate (OR 1.28, CI 95% 0.61 to 2.68; I = 0%; 4 studies, 1000 participants; low-certainty evidence). Gonadotropins with GnRH (gonadotropin-releasing hormone) agonist versus gonadotropins alone (4 studies) No data were available for live birth. The pooled effect of two studies revealed that we are uncertain whether gonadotropins with GnRH agonist lead to a higher multiple pregnancy rate compared to gonadotropins alone (OR 2.53, 95% CI 0.82 to 7.86; I = 0; 2 studies, 264 participants; very low-certainty evidence). Gonadotropins with GnRH antagonist versus gonadotropins alone (14 studies) Three studies reported live birth rate per couple, and we are uncertain whether gonadotropins with GnRH antagonist improve live birth rate compared to gonadotropins (OR 1.5, 95% CI 0.52 to 4.39; I = 81%; 3 studies, 419 participants; very low-certainty evidence). This suggests that if the chance of a live birth following gonadotropins alone is 25.7%, the chance following gonadotropins combined with GnRH antagonist would be between 15.2% and 60.3%. We are also uncertain whether gonadotropins combined with GnRH antagonist lead to a higher multiple pregnancy rate compared with gonadotropins alone (OR 1.30, 95% CI 0.74 to 2.28; I = 0%; 10 studies, 2095 participants; moderate-certainty evidence). Gonadotropins with anti-oestrogens versus gonadotropins alone (2 studies) Neither of the studies reported data for live birth rate. We are uncertain whether gonadotropins combined with anti-oestrogens lead to a higher multiple pregnancy rate compared with gonadotropins alone, based on one study (OR 3.03, 95% CI 0.12 to 75.1; 1 study, 230 participants; low-certainty evidence). Aromatase inhibitors versus gonadotropins (6 studies) Two studies revealed that aromatase inhibitors may decrease live birth rate compared with gonadotropins (OR 0.49, 95% CI 0.34 to 0.71; I=0%; 2 studies, 651 participants; low-certainty evidence). This suggests that if the chance of a live birth following gonadotropins alone is 31.9%, the chance of live birth following aromatase inhibitors would be between 13.7% and 25%. We are uncertain whether aromatase inhibitors compared with gonadotropins lead to a higher multiple pregnancy rate (OR 0.69, 95% CI 0.06 to 8.17; I=77%; 3 studies, 731 participants; very low-certainty evidence). Aromatase inhibitors with gonadotropins versus anti-oestrogens with gonadotropins (8 studies) We are uncertain whether aromatase inhibitors combined with gonadotropins improve live birth rate compared with anti-oestrogens plus gonadotropins (OR 0.99, 95% CI 0.3 8 to 2.54; I = 69%; 3 studies, 708 participants; very low-certainty evidence). This suggests that if the chance of a live birth following anti-oestrogens plus gonadotropins is 13.8%, the chance following aromatase inhibitors plus gonadotropins would be between 5.7% and 28.9%. We are uncertain of the effect of aromatase inhibitors combined with gonadotropins compared to anti-oestrogens combined with gonadotropins on multiple pregnancy rate (OR 1.31, 95% CI 0.39 to 4.37; I = 0%; 5 studies, 901 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
Based on the available results, gonadotropins probably improve cumulative live birth rate compared with anti-oestrogens (moderate-certainty evidence). Gonadotropins may also improve cumulative live birth rate when compared with aromatase inhibitors (low-certainty evidence). From the available data, there is no convincing evidence that aromatase inhibitors lead to higher live birth rates compared to anti-oestrogens. None of the agents compared lead to significantly higher multiple pregnancy rates. Based on low-certainty evidence, there does not seem to be a role for different combined therapies, nor for adding GnRH agonists or GnRH antagonists in IUI programs.
Topics: Female; Fertilization in Vitro; Humans; Infertility, Female; Insemination; Insemination, Artificial; Live Birth; Male; Ovulation Induction; Pregnancy; Pregnancy Rate
PubMed: 34739136
DOI: 10.1002/14651858.CD005356.pub3 -
BJOG : An International Journal of... Jan 2019Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during... (Meta-Analysis)
Meta-Analysis
Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results.
OBJECTIVE
The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles.
SEARCH STRATEGY
Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017.
SELECTION CRITERIA
Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group.
DATA COLLECTION AND ANALYSIS
The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests.
MAIN RESULTS
Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected.
CONCLUSION
Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles.
TWEETABLE ABSTRACT
Pituitary block with GnRH antagonists does not improve the success of IUI cycles.
Topics: Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Insemination, Artificial; Live Birth; Male; Ovulation Induction; Pituitary Gland; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic
PubMed: 29862633
DOI: 10.1111/1471-0528.15269 -
AIDS and Behavior Sep 2018We conducted a systematic review of safer conception strategies (SCS) for HIV-affected couples in sub-Saharan Africa to inform evidence-based safer conception...
We conducted a systematic review of safer conception strategies (SCS) for HIV-affected couples in sub-Saharan Africa to inform evidence-based safer conception interventions. Following PRISMA guidelines, we searched fifteen electronic databases using the following inclusion criteria: SCS research in HIV-affected couples; published after 2007; in sub-Saharan Africa; primary research; peer-reviewed; and addressed a primary topic of interest (SCS availability, feasibility, and acceptability, and/or education and promotion). Researchers independently reviewed each study for eligibility using a standardized tool. We categorize studies by their topic area. We identified 41 studies (26 qualitative and 15 quantitative) that met inclusion criteria. Reviewed SCSs included: antiretroviral therapy (ART), pre-exposure prophylaxis, timed unprotected intercourse, manual/self-insemination, sperm washing, and voluntary male medical circumcision (VMMC). SCS were largely unavailable outside of research settings, except for general availability (i.e., not specifically for safer conception) of ART and VMMC. SCS acceptability was impacted by low client and provider knowledge about safer conception services, stigma around HIV-affected couples wanting children, and difficulty with HIV disclosure in HIV-affected couples. Couples expressed desire to learn more about SCS; however, provider training, patient education, SCS promotions, and integration of reproductive health and HIV services remain limited. Studies of provider training and couple-based education showed improvements in communication around fertility intentions and SCS knowledge. SCS are not yet widely available to HIV-affected African couples. Successful implementation of SCS requires that providers receive training on effective SCS and provide couple-based safer conception counseling to improve disclosure and communication around fertility intentions and reproductive health.
Topics: Africa South of the Sahara; Anti-Retroviral Agents; Circumcision, Male; Counseling; Disclosure; Female; Fertility; Fertilization; HIV Infections; Health Services Accessibility; Heterosexuality; Humans; Insemination, Artificial; Intention; Male; Pre-Exposure Prophylaxis; Preconception Care; Reproductive Behavior; Reproductive Health; Sexual Partners; Social Stigma
PubMed: 29869184
DOI: 10.1007/s10461-018-2170-x -
The Cochrane Database of Systematic... Jul 2021In subfertile couples, couples who have tried to conceive for at least one year, intrauterine insemination (IUI) with ovarian hyperstimulation (OH) is one of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In subfertile couples, couples who have tried to conceive for at least one year, intrauterine insemination (IUI) with ovarian hyperstimulation (OH) is one of the treatment modalities that can be offered. When IUI is performed a second IUI in the same cycle might add to the chances of conceiving. In a previous update of this review in 2010 it was shown that double IUI increases pregnancy rates when compared to single IUI. Since 2010, different clinical trials have been published with differing conclusions about whether double IUI increases pregnancy rates compared to single IUI.
OBJECTIVES
To determine the effectiveness and safety of double intrauterine insemination (IUI) compared to single IUI in stimulated cycles for subfertile couples.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase and CINAHL in July 2020 and LILACS, Google scholar and Epistemonikos in February 2021, together with reference checking and contact with study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled, parallel trials of double versus single IUIs in stimulated cycles in subfertile couples.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information.
MAIN RESULTS
We identified in nine studies involving subfertile women. The evidence was of low quality; the main limitations were unclear risk of bias, inconsistent results for some outcomes and imprecision, due to small trials with imprecise results. We are uncertain whether double IUI improves live birth rate compared to single IUI (odds ratio (OR) 1.15, 95% confidence interval (CI) 0.71 to 1.88; I = 29%; studies = 3, participants = 468; low quality evidence). The evidence suggests that if the chance of live birth following single IUI is 16%, the chance of live birth following double IUI would be between 12% and 27%. Performing a sensitivity analysis restricted to only randomised controlled trials (RCTs) with low risk of selection bias showed similar results. We are uncertain whether double IUI reduces miscarriage rate compared to single IUI (OR 1.78, 95% CI 0.98 to 3.24; I = 0%; studies = 6, participants = 2363; low quality evidence). The evidence suggests that chance of miscarriage following single IUI is 1.5% and the chance following double IUI would be between 1.5% and 5%. The reported clinical pregnancy rate per woman randomised may increase with double IUI group (OR 1.51, 95% CI 1.23 to 1.86; I = 34%; studies = 9, participants = 2716; low quality evidence). This result should be interpreted with caution due to the low quality of the evidence and the moderate inconsistency. The evidence suggests that the chance of a pregnancy following single IUI is 14% and the chance following double IUI would be between 16% and 23%. We are uncertain whether double IUI affects multiple pregnancy rate compared to single IUI (OR 2.04, 95% CI 0.91 to 4.56; I = 8%; studies = 5; participants = 2203; low quality evidence). The evidence suggests that chance of multiple pregnancy following single IUI is 0.7% and the chance following double IUI would be between 0.85% and 3.7%. We are uncertain whether double IUI has an effect on ectopic pregnancy rate compared to single IUI (OR 1.22, 95% CI 0.35 to 4.28; I = 0%; studies = 4, participants = 1048; low quality evidence). The evidence suggests that the chance of an ectopic pregnancy following single IUI is 0.8% and the chance following double IUI would be between 0.3% and 3.2%.
AUTHORS' CONCLUSIONS
Our main analysis, of which the evidence is low quality, shows that we are uncertain if double IUI improves live birth and reduces miscarriage compared to single IUI. Our sensitivity analysis restricted to studies of low risk of selection bias for both outcomes is consistent with the main analysis. Clinical pregnancy rate may increase in the double IUI group, but this should be interpreted with caution due to the low quality evidence. We are uncertain whether double IUI has an effect on multiple pregnancy rate and ectopic pregnancy rate compared to single IUI.
Topics: Abortion, Spontaneous; Bias; Confidence Intervals; Female; Humans; Infertility, Female; Insemination, Artificial, Homologous; Live Birth; Male; Odds Ratio; Ovulation Induction; Pregnancy; Pregnancy Rate; Pregnancy, Ectopic; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Retreatment; Selection Bias
PubMed: 34260059
DOI: 10.1002/14651858.CD003854.pub2 -
Fertility and Sterility Feb 2020To compare live birth and multiple gestation in patients diagnosed with unexplained infertility undergoing intrauterine insemination after ovarian stimulation (OS-IUI)... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare live birth and multiple gestation in patients diagnosed with unexplained infertility undergoing intrauterine insemination after ovarian stimulation (OS-IUI) with oral medications versus gonadotropins.
DESIGN
Systemic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Patients undergoing OS-IUI for treatment of unexplained infertility.
INTERVENTION(S)
Clomiphene, letrozole, or gonadotropins for OS-IUI.
MAIN OUTCOME MEASURE(S)
Live birth and multiple gestation.
RESULT(S)
Eight total trials were identified that met the inclusion criteria and comprised 2,989 patients undergoing 6,590 cycles. One study reported a significant increase in both live births and multiple gestations with the use of gonadotropins, two studies found an increased likelihood of live birth with the use of gonadotropins, and two studies found an increased risk of twins with gonadotropins. The relative risk of live birth in subjects receiving gonadotropins was 1.09. The relative risk of multiple gestation in subjects receiving gonadotropins was 1.06. Clinical pregnancy was higher in protocols with lax cancellation policies or higher gonadotropin doses, with subsequent increased relative risks of multiple gestations of 1.20 and 1.15, respectively. Singleton births per subject were similar between the two groups. The results did not change in per-protocol, per cycle, or fixed-effect model sensitivity analyses.
CONCLUSION(S)
For every birth gained with the use of gonadotropins, a similar increased risk of multiple gestation occurs. The randomized data do not support the use of gonadotropin for OS-IUI in women with unexplained infertility.
CLINICAL TRIAL REGISTRATION NUMBER
Prospero CRD4201911998.
Topics: Administration, Oral; Adolescent; Adult; Clomiphene; Female; Fertility; Fertility Agents, Female; Gonadotropins; Humans; Infertility; Insemination, Artificial; Letrozole; Live Birth; Ovary; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome; Young Adult
PubMed: 31973903
DOI: 10.1016/j.fertnstert.2019.09.042 -
Journal of Dairy Science May 2017Presynchronization of cows with 2 injections of prostaglandin administered 14 d apart (Presynch-Ovsynch) is a widely adopted procedure to increase pregnancy per... (Meta-Analysis)
Meta-Analysis
Evaluation of prostaglandin F versus prostaglandin F plus gonadotropin-releasing hormone as Presynch methods preceding an Ovsynch in lactating dairy cows: A meta-analysis.
Presynchronization of cows with 2 injections of prostaglandin administered 14 d apart (Presynch-Ovsynch) is a widely adopted procedure to increase pregnancy per artificial insemination (P/AI) at first service. Recently, a presynchronization protocol including GnRH and PGF (Double-Ovsynch; GnRH, 7 d, PGF, 3 d, GnRH) followed 7 d later by an Ovsynch protocol was introduced to overcome the limitations of PGF-based protocols for presynchronization of anovular cows and to precisely set up cows on d 7 of the estrous cycle when the Ovsynch is initiated. A systematic review of the literature and a meta-analytical assessment was performed with the objective to compare the reproductive performance of lactating dairy cows presynchronized with these 2 protocols for the first timed AI (TAI) considering parity-specific effects. A fixed or a random effects meta-analysis was used based on the heterogeneity among the experimental groups. Reproductive outcomes of interest were P/AI measured on d 32 (28-42) and pregnancy loss between d 32 and 60 (42-74) of gestation. A total of 25 articles with 27 experimental groups from 63 herds including 21,046 cows submitted to first TAI using either a Presynch-Ovsynch or a Double-Ovsynch protocol were reviewed. Results for P/AI were then categorized by parity if available. Information was available for P/AI for 7,400 and 10,999 primiparous and multiparous cows, respectively. Information regarding pregnancy loss was available for 7,477 cows. In the random effects model for all cows, the overall proportion of P/AI was 41.7% [95% confidence interval (CI): 39.1-44.3; n = 8,213] and 46.2% (95% CI: 41.9-50.5; n = 12,833) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for primiparous cows, the overall proportion of P/AI was 43.4% (95% CI: 36.2-47.7; n = 2,614) and 51.4% (95% CI: 47.4-55.4; n = 4,786) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. In the random effects model for multiparous cows, the overall proportion of P/AI was 39.2% (95% CI: 36.2-42.3; n = 3,411) and 41.4% (95% CI: 36.4-46.4; n = 7,588) on d 32 after TAI for Presynch-Ovsynch and Double-Ovsynch, respectively. The overall proportion of pregnancy loss was 11.3% (95% CI: 7.6-15.7; n = 3,247) and 11.7% (95% CI: 9.3-14.3; n = 4,230) on d 60 after AI for Presynch-Ovsynch to and Double-Ovsynch, respectively. Substantial heterogeneity existed among the experimental groups regarding P/AI and pregnancy loss. In summary, a benefit was detected for P/AI in primiparous cows presynchronized with a Double-Ovsynch protocol for the first TAI, but this benefit was not observed in multiparous cows.
Topics: Abortion, Veterinary; Animals; Cattle; Dinoprost; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Lactation; Progesterone
PubMed: 28318589
DOI: 10.3168/jds.2016-11956 -
Reproduction & Fertility May 2024Chronic endometritis (CE) in humans is asymptomatic inflammation of the endometrium, associated with poor reproductive outcomes. Similarly asymptomatic endometrial...
Chronic endometritis (CE) in humans is asymptomatic inflammation of the endometrium, associated with poor reproductive outcomes. Similarly asymptomatic endometrial inflammation in cows, termed subclinical endometritis (SCE), is associated with adverse reproductive outcomes. While the pathophysiology and treatment options for CE in humans remains poorly defined, the financial implications of SCE in dairy cows mean it has been intensively researched. We performed a systematic review with an emergent theme thematic analysis of studies of SCE in cows, to determine potential areas of interest in human CE research. A literature search for studies of subclinical endometritis in cows published between 1990 and November 2021 was performed across Embase, Medline, Scopus and CINAHL. Studies of symptomatic or clinical endometritis were excluded. Thematic analysis across two broad themes were explored: diagnostic methods and pathophysiology of SCE. In total, 44 bovine studies were included. 12 studies reported on diagnostic methodology. The primary emergent theme was the use of cytology for the diagnosis of SCE. This method has a lower sensitivity than histopathology but is less invasive and more specific than alternative techniques of ultrasound, vaginoscopy, or metabolic markers. The subthemes related to pathophysiology were identified as type of endometritis, metabolic stress, artificial insemination, infective causes, and altered cellular pathways. Despite the lack of symptoms, cellular pathways of inflammation including NFkB, MAPK, and inflammasomes were found to be activated. The key themes related to the diagnosis and pathophysiology of SCE in cows identified in this systematic review highlight potential areas for future research into human CE.
PubMed: 38734031
DOI: 10.1530/RAF-23-0035 -
Journal of Obstetrics and Gynaecology... Mar 2018Physical activity (PA) behaviours after assisted reproductive technology (ART) may influence its success. Bedrest is frequently recommended immediately after...
Physical activity (PA) behaviours after assisted reproductive technology (ART) may influence its success. Bedrest is frequently recommended immediately after intrauterine insemination (IUI) or embryo transfer (ET), and women are also commonly advised to restrict PA after ART. However, these recommendations are not grounded on evidence-based information. The purpose of this systematic review was to assess the impact of PA behaviours during ART on ART success (positive pregnancy test, clinical pregnancy, live birth). A systematic search of the literature was conducted in PubMed, Medline, SPORTdiscus, and CINAHL. The Grading of Recommendations Assessment, Development, and Evaluation system was applied to studies by clinical outcome and used to rate quality of evidence. Twelve studies were included in the review. Our findings suggest that the effect of bedrest immediately after IUI or ET on ART success depends on the procedure used, with favourable effects after IUI ("moderate" quality evidence on clinical pregnancy) but no effect, and even possible unfavourable effects, after ET ("very low" quality evidence on positive pregnancy test and clinical pregnancy). "Very low" quality evidence suggested a decreased live birth rate with bedrest after ET (n = 1) but an increased rate with bedrest after IUI (n = 1). "Very low" quality of evidence suggested no deleterious effect of moderate PA on clinical pregnancy and live birth after ET. On the basis of our findings, studies with more rigourous design and methodology, and considering live birth as an outcome, are needed to provide further evidence on the most appropriate PA behaviours women should adopt to improve ART success.
Topics: Bed Rest; Birth Rate; Embryo Transfer; Exercise; Female; Humans; Insemination, Artificial; Treatment Outcome
PubMed: 28826643
DOI: 10.1016/j.jogc.2017.07.001