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Archives of Gynecology and Obstetrics Apr 2022IUI + COH is widely used in cases of unexplained infertility before resorting to IVF. Debate continues about what should be the first-line treatment for couples with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
IUI + COH is widely used in cases of unexplained infertility before resorting to IVF. Debate continues about what should be the first-line treatment for couples with unexplained infertility.
OBJECTIVES
This systematic review assessed the relative efficacy of IUI + COH compared with IVF in couples with unexplained infertility.
SEARCH STRATEGY
We searched Medline, Embase, CIHNL, Pscy Info, and Cochrane Library from 1980 to November 2019.
SELECTION CRITERIA
Only RCTs published articles in full text with female patients aged 18-43 years and diagnosed with unexplained infertility were included.
DATA COLLECTION AND ANALYSIS
Two authors reviewed citations from primary search independently and any disagreement was resolved by mutual discussion and consultation with a third author.
MAIN RESULT
In total, eight RCTs were included. The quality of evidence was moderate to low due to inconsistency across the trials and imprecision. The pooled result showed that IVF was associated with a statistically significant higher live birth rate (RR 1.53, 95% CI 1.01-2.32, P < 0.00001 I = 86%) with no significant difference in multiple pregnancy rate or OHSS rate. Sensitivity analysis based on women's age and a history of previous IUI or IVF treatment showed no significant difference in the live birth rates (RR 1.01, 95% CI 0.88-1.15, I = 0%, 3 RCTs) in treatment-naïve women younger than 38 years. In women over 38 years, the live birth rates were significantly higher in the IVF group (RR 2.15, 95% CI 1.16-4.0, I = 42%, 1 RCT).
CONCLUSION
Further research using a standardised treatment protocol and taking into account important prognostic variables and cumulative live birth rates from fresh IVF and all sibling frozen embryos is required to further guide clinical practice.
Topics: Adolescent; Adult; Female; Fertilization in Vitro; Humans; Infertility; Insemination, Artificial; Live Birth; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Young Adult
PubMed: 34636983
DOI: 10.1007/s00404-021-06277-3 -
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 -
European Journal of Obstetrics,... Aug 2021There is a great controversy regarding the benefits of ultrasound-guided intrauterine insemination (IUI) in improving pregnancy rates. Thus, we aimed to compare... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
There is a great controversy regarding the benefits of ultrasound-guided intrauterine insemination (IUI) in improving pregnancy rates. Thus, we aimed to compare ultrasound-guided IUI versus classical IUI regarding the pregnancy rates improvement.
METHODS
A systematic search was done in Cochrane Library, PubMed, ISI web of science, and Scopus during June 2021. We selected randomized clinical trials (RCTs) that compared ultrasound-guided IUI versus classical IUI in different pregnancy outcomes. We extracted the available data from included studies and pooled them in a meta-analysis model using RevMan software. Our primary outcome was clinical pregnancy rate. Our secondary outcomes were miscarriage, live birth rates, and incidence of difficulty reported during the procedure. The overall quality of evidence was assessed through GRADEpro GDT software.
RESULTS
Seven RCTs met our inclusion criteria with a total number of 1338 patients. We found that ultrasound-guided IUI significantly improved the clinical pregnancy rate when compared to the classical group (RR = 1.33, 95% CI [1.05, 1.68], p = 0.02). However, there were no significant differences between both groups in terms of miscarriage and live birth rates. Ultrasound-guided IUI significantly reduced the incidence of difficulty reported during the procedure (RR = 0.42, 95% CI [0.21, 0.84], p = 0.01). The GRADEpro GDT tool showed high quality of evidence for the evaluated outcomes.
CONCLUSIONS
There is evidence of high quality that ultrasound-guided IUI improves the pregnancy rate and reduces the incidence of difficulty reported during the procedure.
Topics: Female; Fertilization in Vitro; Humans; Insemination; Insemination, Artificial; Live Birth; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic
PubMed: 34242930
DOI: 10.1016/j.ejogrb.2021.06.039 -
Human Reproduction Update Jan 2021Registry data from the Human Fertilisation and Embryology Authority (HFEA) show an increase of 40% in IUI and 377% in IVF cases using donor sperm between 2006 and 2016. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Registry data from the Human Fertilisation and Embryology Authority (HFEA) show an increase of 40% in IUI and 377% in IVF cases using donor sperm between 2006 and 2016.
OBJECTIVE AND RATIONALE
The objective of this study was to establish whether pregnancies conceived using donor sperm are at higher risk of obstetric and perinatal complications than those conceived with partner sperm. As more treatments are being carried out using donor sperm, attention is being given to obstetric and perinatal outcomes, as events in utero and at delivery have implications for long-term health. There is a need to know if there is any difference in the outcomes of pregnancies between those conceived using donor versus partner sperm in order to adequately inform and counsel couples.
SEARCH METHODS
We performed a systematic review and meta-analysis of the outcomes of pregnancies conceived using donor sperm compared with partner sperm. Searches were performed in the OVID MEDLINE, OVID Embase, CENTRAL and CINAHL databases, including all studies published before 11 February 2019. The search strategy involved search terms for pregnancy, infant, donor sperm, heterologous artificial insemination, donor gametes, pregnancy outcomes and perinatal outcomes. Studies were included if they assessed pregnancies conceived by any method using, or infants born from, donor sperm compared with partner sperm and described early pregnancy, obstetric or perinatal outcomes. The Downs and Black tool was used for quality and bias assessment of studies.
OUTCOMES
Of 3391 studies identified from the search, 37 studies were included in the review and 36 were included in the meta-analysis. For pregnancies conceived with donor sperm, versus partner sperm, there was an increase in the relative risk (RR) (95% CI) of combined hypertensive disorders of pregnancy: 1.44 (1.17-1.78), pre-eclampsia: 1.49 (1.05-2.09) and small for gestational age (SGA): 1.42 (1.17-1.79) but a reduced risk of ectopic pregnancy: 0.69 (0.48-0.98). There was no difference in the overall RR (95% CI) of miscarriage: 0.94 (0.80-1.11), gestational diabetes: 1.49 (0.62-3.59), pregnancy-induced hypertension (PIH): 1.24 (0.87-1.76), placental abruption: 0.65 (0.04-10.37), placenta praevia: 1.19 (0.64-2.21), preterm birth: 0.98 (0.88-1.08), low birth weight: 0.97 (0.82-1.15), high birthweight: 1.28 (0.94-1.73): large for gestational age (LGA): 1.01 (0.84-1.22), stillbirth: 1.23 (0.97-1.57), neonatal death: 0.79 (0.36-1.73) and congenital anomaly: 1.15 (0.86-1.53).
WIDER IMPLICATIONS
The majority of our findings are reassuring, except for the mild increased risk of hypertensive disorders of pregnancy and SGA in pregnancies resulting from donor sperm. However, the evidence for this is limited and should be interpreted with caution because the evidence was based on observational studies which varied in their quality and risk of bias. Further high-quality population-based studies reporting obstetric outcomes in detail are required to confirm these findings.
Topics: Female; Fertilization in Vitro; Humans; Infant, Newborn; Male; Placenta; Pregnancy; Pregnancy Outcome; Premature Birth; Spermatozoa
PubMed: 33057599
DOI: 10.1093/humupd/dmaa030 -
Medicine Jul 2020With the medical advancement some studies put forward that letrozole (LE), a specific aromatase inhibitor with the function of reducing oestrogen synthesis, has recently... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of clomiphene and letrozole for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A systematic review and meta-analysis.
BACKGROUND
With the medical advancement some studies put forward that letrozole (LE), a specific aromatase inhibitor with the function of reducing oestrogen synthesis, has recently been applied as a potentially better alternative compared with clomiphene citrate (CC), owing to that it has a superior efficacy as compared with CC in patients of unexplained infertility undergoing intrauterine insemination (IUI). However, there is no one study can clear and definite whether LE can replace the CC as first line drug.
OBJECTIVE
Our objective is to compare the LE with CC in the induction of ovulation in patients with unexplained infertility IUI.
METHOD
Searching databases consist of all kinds of searching tools, such as Medline, The Cochrane Library, Embase, PubMed, etc. All the include studies should meet our demand of this meta-analysis: RESULT:: Based on the current meta-analysis, we rigorously consider that LE has a likelihood to improve dominant follicles (MD= -0.56, I= 100%, P= .04; MD= -0.39, I= 73%, P = .0003, respectively) and reduces the miscarriage rate (RR= 0.61, I= 0%, P = .03). There is no significant differences between the 2 groups in The total rate of pregnancy, pregnancy rate per cycle, multiple pregnancy and endometrial thickness. (RR= 1.06, I= 11%, P = .38; RR= 1.09, I= 7%, P = .32; RR= 0.79, I= 0%, P = .46; respectively) CONCLUSION:: Combined with the results of current systematic review and meta-analysis through subgroup analysis and sensitivity analysis, we can be cautious: in general, compared with CC, LE is an effective treatment in the IUI cycle, has a likelihood to improve dominant follicles and reduces the miscarriage rate.
Topics: Clomiphene; Female; Fertility Agents, Female; Humans; Infertility, Female; Insemination, Artificial; Letrozole; Superovulation
PubMed: 32756085
DOI: 10.1097/MD.0000000000021006 -
The Cochrane Database of Systematic... Mar 2020Intra-uterine insemination (IUI) is a widely-used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
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.
OBJECTIVES
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.
SEARCH METHODS
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.
SELECTION CRITERIA
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.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, quality assessment and data extraction. Primary review outcomes were live birth rate and multiple pregnancy rate.
MAIN RESULTS
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).
AUTHORS' CONCLUSIONS
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.
Topics: Abortion, Spontaneous; Coitus; Female; Fertile Period; Fertility Agents, Female; Humans; Infertility; Insemination, Artificial; Live Birth; Male; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate; Pregnancy, Multiple; Randomized Controlled Trials as Topic; Time Factors; Watchful Waiting
PubMed: 32124980
DOI: 10.1002/14651858.CD001838.pub6 -
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 -
European Journal of Obstetrics,... Jan 2020There is a growing body of literature that recognizes the importance of sperm DNA fragmentation as a candidate test for the assessment of sperm function and thus male... (Meta-Analysis)
Meta-Analysis
There is a growing body of literature that recognizes the importance of sperm DNA fragmentation as a candidate test for the assessment of sperm function and thus male reproductive potential. Research on the subject has mostly been focused on couples undergoing IVF/ICSI treatment whilst much uncertainty still exists about the relationship between sperm DNA fragmentation and IUI. This study systematically reviews the literature, aiming to define the value of sperm DNA fragmentation measurement in predicting clinical pregnancy outcome in couples undergoing intra-uterine insemination From inception until March 2018, the relevant databases were searched for studies investigating the relationship between sperm DNA fragmentation as measured by SCSA, TUNEL, SCD or Comet assay and pregnancy outcome after IUI. The Quality in Prognosis Studies (QUIPS) tool was utilized for quality assessment. This review is reported according to the 2009 PRISMA statement. The literature search resulted in 433 studies of which we finally retained nine studies for the qualitative analysis and four studies for the meta-analysis, accounting for 940 IUI cycles. In summary, the observed effect of low sperm DNA fragmentation on clinical pregnancy after IUI as analyzed with the random effects model reveals a relative risk of 3.15 (95% CI: 1.46-6.79; I2 = 13.1%) and pooled sensitivity and specificity of respectively 94% (95% CI: 0.88; 0.97) and 19% (95% CI: 0.14; 0.26). Taken together, the included studies show a limited capacity of sperm DNA fragmentation in discriminating between couples who will benefit from the test, namely in either predicting IUI outcome or in advising for or against IUI as first choice of treatment instead of advancing to more invasive medically assisted reproduction. This review has thrown up many questions in need of further investigation. As such, future studies might explore issues such as determining relevant cut-off values for prediction of spontaneous pregnancy and pregnancy after IUI as well as the assessment of the stability of the test over time and before and after density gradient centrifugation.
Topics: DNA; DNA Fragmentation; Female; Humans; Insemination, Artificial; Male; Pregnancy; Pregnancy Outcome; Spermatozoa
PubMed: 31707171
DOI: 10.1016/j.ejogrb.2019.10.005