Timed intercourse for couples trying to conceive Gibbons, Tatjana; Gibbons, Tatjana; Reavey, Jane ...
Cochrane database of systematic reviews,
09/2023, Letnik:
2023, Številka:
9
Journal Article
Recenzirano
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Background
Many factors influence fertility, one being the timing of intercourse. The 'fertile window' describes a stage in the cycle when conception can occur and is approximately five days before ...to several hours after ovulation. 'Timed intercourse' is the practice of prospectively identifying ovulation and, thus, the fertile window to increase the likelihood of conception. Methods of predicting ovulation include urinary hormone measurement (luteinising hormone (LH) and oestrogen), fertility awareness‐based methods (FABM) (including tracking basal body temperatures, cervical mucus monitoring, calendar charting/tracking apps), and ultrasonography. However, there are potentially negative aspects associated with ovulation prediction, including stress, time consumption, and cost implications of purchasing ovulation kits and app subscriptions. This review considered the evidence from randomised controlled trials (RCTs) evaluating the use of timed intercourse (using ovulation prediction) on pregnancy outcomes.
Objectives
To evaluate the benefits and risks of ovulation prediction methods for timing intercourse on conception in couples trying to conceive.
Search methods
We searched the Cochrane Gynaecology and Fertility (CGF) Group Specialised Register, CENTRAL, MEDLINE, and Embase in January 2023. We also checked the reference lists of relevant studies and searched trial registries for any additional trials.
Selection criteria
We included RCTs that compared methods of timed intercourse using ovulation prediction to other forms of ovulation prediction or intercourse without ovulation prediction in couples trying to conceive.
Data collection and analysis
We used standard methodological procedures recommended by Cochrane to select and analyse studies in this review. The primary review outcomes were live birth and adverse events (such as depression and stress). Secondary outcomes were clinical pregnancy, pregnancy (clinical or positive urinary pregnancy test not yet confirmed by ultrasound), time to pregnancy, and quality of life. We assessed the overall quality of the evidence for the main comparisons using GRADE methods.
Main results
This review update included seven RCTs involving 2464 women or couples. Four of the five studies from the previous review were included in this update, and three new studies were added. We assessed the quality of the evidence as moderate to very low, the main limitations being imprecision, indirectness, and risk of bias.
Urinary ovulation tests versus intercourse without ovulation prediction
Compared to intercourse without ovulation prediction, urinary ovulation detection probably increases the chance of live birth in couples trying to conceive (risk ratio (RR) 1.36, 95% confidence interval (CI) 1.02 to 1.81, 1 RCT, n = 844, moderate‐quality evidence). This suggests that if the chance of a live birth without urine ovulation prediction is 16%, the chance of a live birth with urine ovulation prediction is 16% to 28%. However, we are uncertain whether timed intercourse using urinary ovulation detection resulted in a difference in stress (mean difference (MD) 1.98, 95% CI −0.87 to 4.83, I² = 0%, P = 0.17, 1 RCT, n = 77, very low‐quality evidence) or clinical pregnancy (RR 1.09, 95% CI 0.51 to 2.31, I² = 0%, 1 RCT, n = 148, low‐quality evidence). Similar to the live birth result, timed intercourse using urinary ovulation detection probably increases the chances of clinical pregnancy or positive urine pregnancy test (RR 1.28, 95% CI 1.09 to 1.50, I² = 0, 4 RCTs, n = 2202, moderate‐quality evidence). This suggests that if the chance of a clinical pregnancy or positive urine pregnancy test without ovulation prediction is assumed to be 18%, the chance following timed intercourse with urinary ovulation detection would be 20% to 28%. Evidence was insufficient to determine the effect of urine ovulation tests on time to pregnancy or quality of life.
Fertility awareness‐based methods (FABM) versus intercourse without ovulation prediction
Due to insufficient evidence, we are uncertain whether timed intercourse using FABM resulted in a difference in live birth rate compared to intercourse without ovulation prediction (RR 0.95, 95% CI 0.76 to 1.20, I² = 0%, 2 RCTs, n = 157, low‐quality evidence). We are also uncertain whether FABM affects stress (MD −1.10, 95% CI −3.88 to 1.68, 1 RCT, n = 183, very low‐quality evidence). Similarly, we are uncertain of the effect of timed intercourse using FABM on anxiety (MD 0.5, 95% CI −0.52 to 1.52, P = 0.33, 1 RCT, n = 183, very low‐quality evidence); depression (MD 0.4, 95% CI −0.28 to 1.08, P = 0.25, 1 RCT, n = 183, very low‐quality evidence); or erectile dysfunction (MD 1.2, 95% CI −0.38 to 2.78, P = 0.14, 1 RCT, n = 183, very low‐quality evidence). Evidence was insufficient to detect a benefit of timed intercourse using FABM on clinical pregnancy (RR 1.13, 95% CI 0.31 to 4.07, 1 RCT, n = 17, very low‐quality evidence) or clinical or positive pregnancy test rates (RR 1.08, 95% CI 0.89 to 1.30, 3 RCTs, n = 262, very low‐quality evidence). Finally, we are uncertain whether timed intercourse using FABM affects the time to pregnancy (hazard ratio 0.86, 95% CI 0.53 to 1.38, 1 RCT, n = 140, low‐quality evidence) or quality of life.
No studies assessed the use of timed intercourse with pelvic ultrasonography.
Authors' conclusions
The new evidence presented in this review update shows that timed intercourse using urine ovulation tests probably improves live birth and pregnancy rates (clinical or positive urine pregnancy tests but not yet confirmed by ultrasound) in women under 40, trying to conceive for less than 12 months, compared to intercourse without ovulation prediction. However, there are insufficient data to determine the effects of urine ovulation tests on adverse events, clinical pregnancy, time to pregnancy, and quality of life. Similarly, due to limited data, we are uncertain of the effect of FABM on pregnancy outcomes, adverse effects, and quality of life.
Further research is therefore required to fully understand the safety and effectiveness of timed intercourse for couples trying to conceive. This research should include studies reporting clinically relevant outcomes such as live birth and adverse effects in fertile and infertile couples and utilise various methods to determine ovulation. Only with a comprehensive understanding of the risks and benefits of timed intercourse can recommendations be made for all couples trying to conceive.
Background
Endometriosis is a chronic inflammatory condition that occurs during the reproductive years. It is characterised by endometrium‐like tissue developing outside the uterine cavity. This ...endometriotic tissue development is dependent on oestrogen produced primarily by the ovaries and partially by the endometriotic tissue itself, therefore traditional management has focused on ovarian suppression. In this review we considered the role of modulation of the immune system as an alternative approach. This is an update of a Cochrane Review previously published in 2012.
Objectives
To determine the effectiveness and safety of pentoxifylline in the management of endometriosis.
Search methods
We searched the Cochrane Gynaecology and Fertility (CGF) Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, and AMED on 16 December 2020, together with reference checking and contact with study authors and experts in the field to identify additional studies.
Selection criteria
We included randomised controlled trials (RCTs) comparing pentoxifylline with placebo or no treatment, other medical treatment, or surgery in women with endometriosis. The primary outcomes were live birth rate and overall pain (as measured by a visual analogue scale (VAS) of pain, other validated scales, or dichotomous outcomes) per woman randomised. Secondary outcomes included clinical pregnancy rate, miscarriage rate, rate of recurrence, and adverse events resulting from the pentoxifylline intervention.
Data collection and analysis
Two review authors independently assessed studies against the inclusion criteria, extracted data, and assessed risk of bias, consulting a third review author where required. We contacted study authors as needed. We analysed dichotomous outcomes using Mantel‐Haenszel risk ratios (RRs), 95% confidence intervals (CIs), and a fixed‐effect model. For small numbers of events, we used a Peto odds ratio (OR) with 95% CI instead. We analysed continuous outcomes using the mean difference (MD) between groups presented with 95% CIs. We used the I2 statistic to evaluate heterogeneity amongst studies. We employed the GRADE approach to assess the quality of the evidence.
Main results
We included five parallel‐design RCTs involving a total of 415 women. We included one additional RCT in this update. Three studies did not specify details relating to allocation concealment, and two studies were not blinded. There were also considerable loss to follow‐up, with four studies not conducting intention‐to‐treat analysis. We judged the quality of the evidence as very low.
Pentoxifylline versus placebo
No trials reported on our primary outcomes of live birth rate and overall pain. We are uncertain as to whether pentoxifylline treatment affects clinical pregnancy rate when compared to placebo (RR 1.38, 95% CI 0.91 to 2.10; 3 RCTs, n = 285; I2 = 0%; very low‐quality evidence). The evidence suggests that if the clinical pregnancy rate with placebo is estimated to be 20%, then the rate with pentoxifylline is estimated as between 18% and 43%. We are also uncertain as to whether pentoxifylline affects the recurrence rate of endometriosis (RR 0.84, 95% CI 0.30 to 2.36; 1 RCT, n = 121; very low‐quality evidence) or miscarriage rate (Peto OR 1.99, 95% CI 0.20 to 19.37; 2 RCTs, n = 164; I2 = 0%; very low‐quality evidence). No trials reported on the effect of pentoxifylline on improvement of endometriosis‐related symptoms other than pain or adverse events.
Pentoxifylline versus no treatment
No trials reported on live birth rate. We are uncertain as to whether pentoxifylline treatment affects overall pain when compared to no treatment at one month (MD −0.36, 95% CI −2.12 to 1.40; 1 RCT, n = 34; very low‐quality evidence), two months (MD −1.25, 95% CI −2.67 to 0.17; 1 RCT, n = 34; very low‐quality evidence), or three months (MD −1.60, 95% CI −3.32 to 0.12; 1 RCT, n = 34; very low‐quality evidence). No trials reported on adverse events caused by pentoxifylline or any of our other secondary outcomes.
Pentoxifylline versus other medical therapies
One study (n = 83) compared pentoxifylline to the combined oral contraceptive pill after laparoscopic surgery to treat endometriosis, but could not be included in the meta‐analysis as it was unclear if the data were presented as +/‐ standard deviation and what the duration of treatment was. No trials reported on adverse events caused by pentoxifylline or any of our other secondary outcomes.
Pentoxifylline versus conservative surgical treatment
No study reported on this comparison.
Authors' conclusions
No studies reported on our primary outcome of live birth rate. Due to the very limited evidence, we are uncertain of the effects of pentoxifylline on clinical pregnancy rate, miscarriage rate, or overall pain.
There is currently insufficient evidence to support the use of pentoxifylline in the management of women with endometriosis with respect to subfertility and pain relief outcomes.
Background
Endometriosis is a condition characterised by the presence of ectopic deposits of endometrial‐like tissue outside the uterus, usually in the pelvis. The impact of laparoscopic treatment on ...overall pain is uncertain and a significant proportion of women will require further surgery. Therefore, adjuvant medical therapies following surgery, such as the levonorgestrel‐releasing intrauterine device (LNG‐IUD), have been considered to reduce recurrence of symptoms.
Objectives
To determine the effectiveness and safety of post‐operative LNG‐IUD in women with symptomatic endometriosis.
Search methods
We searched the following databases from inception to January 2021: The Specialised Register of the Cochrane Gynaecology and Fertility Group, CENTRAL (which now includes records from two trial registries), MEDLINE, Embase, PsycINFO, LILACS and Epistemonikos. We handsearched citation lists of relevant publications, review articles, s of scientific meetings and included studies. We contacted experts in the field for information about any additional studies.
Selection criteria
We included randomised controlled trials (RCTs) comparing women undergoing surgical treatment of endometriosis with uterine preservation who were assigned to LNG‐IUD insertion, versus control conditions including expectant management, post‐operative insertion of placebo (inert intrauterine device), or other medical treatment such as gonadotrophin‐releasing hormone agonist (GnRH‐a) drugs.
Data collection and analysis
Two review authors independently selected studies for inclusion, and extracted data to allow for an intention‐to‐treat analysis. For dichotomous data, we calculated the risk ratio (RR) and 95% confidence interval (CI) using the Mantel‐Haenszel fixed‐effect method. For continuous data, we calculated the mean difference (MD) and 95% CI using the inverse variance fixed‐effect method.
Main results
Four RCTs were included, with a total of 157 women. Two studies are ongoing. The GRADE certainty of evidence was very low to low. The certainty of evidence was graded down primarily for serious risk of bias and imprecision.
LNG‐IUD versus expectant management
Overall pain: No studies reported on the primary outcome of overall pain.
Dysmenorrhoea: We are uncertain whether LNG‐IUD improves dysmenorrhoea at 12 months. Data on this outcome were reported on by two RCTs; meta‐analysis was not possible (RCT 1: delta of median visual analogue scale (VAS) 81 versus 50, P = 0.006, n = 55; RCT 2: fall in VAS by 50 (35 to 65) versus 30 (25 to 40), P = 0.021, n = 40; low‐certainty evidence).
Quality of life: We are uncertain whether LNG‐IUD improves quality of life at 12 months. One trial demonstrated a change in total quality of life score with postoperative LNG‐IUD from baseline (mean 61.2 (standard deviation (SD) 14.8) to 12 months (mean 70.3 (SD 16.2) compared to expectant management (baseline 55.1 (SD 17.0) to 57.0 (SD 33.2) at 12 months) (n = 55, P = 0.014, very low‐certainty evidence).
Patient satisfaction: Two studies found higher rates of satisfaction with LNG‐IUD compared to expectant management; however, combining the studies in meta‐analysis was not possible (n = 95, very low‐certainty evidence). One study found 75% (15/20) of those given post‐operative LNG‐IUD were "satisfied" or "very satisfied", compared to 50% (10/20) of those in the expectant management group (RR 1.5, 95% CI 0.90‐2.49, 1 RCT, n=40, very low‐certainty evidence). The second study found that fewer were "very satisfied" in the expectant management group when compared to LNG, but there were no data to include in a meta‐analysis.
Adverse events: One study found a significantly higher proportion of women reporting melasma (n = 55, P = 0.015, very low‐certainty evidence) and bloating (n = 55, P = 0.021, very low‐certainty evidence) following post‐operative LNG‐IUD. There were no differences in other reported adverse events, such as weight gain, acne, and headaches.
LNG‐IUD versus GnRH‐a
Overall pain: No studies reported on the primary outcome of overall pain.
Chronic pelvic pain: We are uncertain whether LNG‐IUD improves chronic pelvic pain at 12 months when compared to GnRH‐a (VAS pain scale) (MD ‐2.0, 95% CI ‐20.2 to 16.2, 1 RCT, n = 40, very low‐certainty evidence).
Dysmenorrhoea: We are uncertain whether LNG‐IUD improves dysmenorrhoea at six months when compared to GnRH‐a (measured as a reduction in VAS pain score) (MD 1.70, 95%.CI ‐0.14 to 3.54, 1 RCT, n = 18, very low‐certainty evidence).
Adverse events: One study suggested that vasomotor symptoms were the most common adverse events reported with patients receiving GnRH‐a, and irregular bleeding in those receiving LNG‐IUD (n = 40, very low‐certainty evidence)
Authors' conclusions
Post‐operative LNG‐IUD is widely used to reduce endometriosis‐related pain and to improve operative outcomes. This review demonstrates that there is no high‐quality evidence to support this practice. This review highlights the need for further studies with large sample sizes to assess the effectiveness of post‐operative adjuvant hormonal IUD on the core endometriosis outcomes (overall pain, most troublesome symptom, and quality of life).
Background
Follicular aspiration under transvaginal ultrasound guidance is routinely performed as part of assisted reproductive technology (ART) to retrieve oocytes for in vitro fertilisation (IVF). ...The process involves aspiration of the follicular fluid followed by the introduction of flush, typically culture media, back into the follicle followed by re‐aspiration. However, there is a degree of controversy as to whether this intervention yields a larger number of oocytes and is hence associated with greater potential for pregnancy than aspiration only.
Objectives
To assess the safety and efficacy of follicular flushing as compared with aspiration only performed in women undergoing ART.
Search methods
We searched the following electronic databases up to 13 July 2021: the Cochrane Gynaecology and Fertility Specialised Register of Controlled Trials, CENTRAL (containing output from two trial registries and CINAHL), MEDLINE, Embase, and PsycINFO. We also searched LILACS, Google Scholar, and Epistemonikos. We reviewed the reference lists of relevant papers and contacted experts in the field to identify further relevant studies.
Selection criteria
We included randomised controlled trials (RCTs) that compared follicular aspiration and flushing with aspiration alone in women undergoing ART using their own gametes. Primary outcomes were live birth rate and miscarriage rate per woman randomised.
Data collection and analysis
Two review authors independently assessed studies identified by search against the inclusion criteria, extracted data, and assessed risk of bias. A third review author was consulted if required. We contacted study authors as needed. We analysed dichotomous outcomes using Mantel‐Haenszel odds ratios (ORs), 95% confidence intervals (CIs), and a fixed‐effect model, and we analysed continuous outcomes using mean differences (MDs) between groups presented with 95% CIs. We examined the heterogeneity of studies via the I2 statistic. We assessed the certainty of evidence using the GRADE approach.
Main results
We included 15 studies with a total of 1643 women. Fourteen studies reported outcomes per woman randomised, and one study reported outcomes per ovary. No studies were at low risk of bias across all domains; the main limitation was lack of blinding. The certainty of the evidence ranged from moderate to very low, and was downgraded for risk of bias, imprecision, and inconsistency.
We are uncertain of the effect of follicular flushing on live birth rate compared to aspiration alone (OR 0.93, 95% CI 0.59 to 1.46; 4 RCTs; n = 467; I2 = 0%; moderate‐certainty evidence). This suggests that with a live birth rate of approximately 30% with aspiration alone, the equivalent live birth rate with follicular flushing lies between 20% and 39%. We are uncertain of the effect of follicular flushing on miscarriage rate compared to aspiration alone (OR 1.98, 95% CI 0.18 to 22.22; 1 RCT; n = 164; low‐certainty evidence). This suggests that with a miscarriage rate of approximately 1% with aspiration alone, the equivalent miscarriage rate with follicular flushing lies between 0% and 22%.
We are uncertain of the effect of follicular flushing on oocyte yield (MD −0.47 oocytes, 95% CI −0.72 to −0.22; 9 RCTs; n = 1239; I2 = 61%; very low‐certainty evidence); total number of embryos (MD −0.10 embryos, 95% CI −0.34 to 0.15; 2 RCTs; n = 160; I2 = 58%; low‐certainty evidence); and clinical pregnancy rate (OR 1.12, 95% CI 0.85 to 1.51; 7 RCTs; n = 939; I2 = 46%; low‐certainty evidence). The duration of the retrieval process may be longer with flushing (MD 175.44 seconds, 95% CI 152.57 to 198.30; 7 RCTs; n = 785; I2 = 87%; low‐certainty evidence). It was not possible to perform a meta‐analysis for adverse events, although individual studies reported on outcomes ranging from depression and anxiety to pain and pelvic organ injury.
Authors' conclusions
The effect of follicular flushing on both live birth and miscarriage rates compared with aspiration alone is uncertain. Although the evidence does not permit any firm conclusions on the impact of follicular flushing on oocyte yield, total number of embryos, number of cryopreserved embryos, or clinical pregnancy rate, it may be that the procedure itself takes longer than aspiration alone. The evidence was insufficient to permit any firm conclusions with respect to adverse events or safety.
Abstract
Numerous chronic diseases have a substantial hereditary component. Recent advances in human genetics have allowed the extent of this to be quantified via genome-wide association studies, ...producing polygenic risk scores (PRS), which can then be applied to individuals to estimate their risk of developing a disease in question. This technology has recently been applied to embryo selection in the setting of IVF and preimplantation genetic testing, with limited data to support its utility. Furthermore, there are concerns that the inherent limitations of PRS makes it ill-suited for use as a screening test in this setting. There are also serious ethical and moral questions associated with this technology that are yet to be addressed. We conclude that further research and ethical reflection are required before embryo selection based on PRS is offered to patients outside of the research setting.
Background
Follicular aspiration under transvaginal ultrasound guidance is routinely performed as part of assisted reproductive technology (ART) to retrieve oocytes for in vitro fertilisation (IVF). ...However, controversy as to whether follicular flushing following aspiration yields a larger number of oocytes and hence is associated with greater potential for pregnancy than aspiration only is ongoing.
Objectives
To assess the safety and efficacy of follicular flushing as compared with aspiration only performed in women undergoing ART.
Search methods
We searched the following electronic databases up to 18 July 2017: Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, the CENTRAL Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We also searched the trial registries ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform to identify ongoing and registered trials up to 4 July 2017. We reviewed the reference lists of reviews and retrieved studies to identify further potentially relevant studies.
Selection criteria
We included randomised controlled trials (RCTs) that compared follicular aspiration and flushing with aspiration alone in women undergoing ART using their own gametes. Primary outcomes were live birth rate and miscarriage rate per woman randomised.
Data collection and analysis
Two independent review authors assessed studies against the inclusion criteria, extracted data, and assessed risk of bias. A third review author was consulted if required. We contacted study authors as required. We analysed dichotomous outcomes using Mantel‐Haenszel odds ratios (ORs), 95% confidence intervals (CIs), and a fixed‐effect model, and we analysed continuous outcomes using mean differences (MDs) between groups presented with 95% CIs. We examined the heterogeneity of studies via the I2 statistic. We assessed the quality of evidence by using GRADE (Grades of Recommendation, Assessment, Development and Evaluation) criteria.
Main results
We included ten studies, with a total of 928 women. All included studies reported outcomes per woman randomised. We assessed no studies as being at low risk of bias across all domains and found that the main limitation was lack of blinding. Using the GRADE method, we determined that the quality of the evidence ranged from moderate to very low, and we identified issues arising from risk of bias, imprecision, and inconsistency.
Comparing follicular flushing to aspiration alone revealed probably little or no difference in the live birth rate (OR 0.95, 95% CI 0.58 to 1.56; three RCTs; n = 303; I2 = 30%; moderate‐quality evidence). This suggests that with a live birth rate of approximately 41% with aspiration alone, the equivalent live birth rate with follicular flushing is likely to lie between 29% and 52%. None of the included studies reported on the primary outcome of miscarriage rate.
Data show probably little or no difference in oocyte yield (MD ‐0.28 oocytes, 95% CI ‐0.64 to 0.09; six RCTs; n = 708; I2 = 0%; moderate‐quality evidence). Very low‐quality evidence suggests that the duration of oocyte retrieval was longer in the follicular flushing group than in the aspiration only group (MD 166.01 seconds, 95% CI 141.96 to 190.06; six RCTs; n = 714; I2 = 88%). We found no evidence of a difference in the total number of embryos per woman randomised (MD ‐0.10 embryos, 95% CI ‐0.34 to 0.15; two RCTs; n = 160; I2 = 58%; low‐quality evidence) and no evidence of a difference in the number of embryos cryopreserved (meta‐analysis not possible). Data show probably little or no difference in the clinical pregnancy rate (OR 1.07, 95% CI 0.78 to 1.46; five RCTs; n = 704; I2 = 49%; moderate‐quality evidence). Only two studies reported on adverse outcomes: One reported no differences in patient‐reported adverse outcomes (depression, anxiety, and stress), and the other reported no differences in needle blockage, vomiting, and hypotension. No studies reported on safety.
Authors' conclusions
This review suggests that follicular flushing probably has little or no effect on live birth rates compared with aspiration alone. None of the included trials reported on effects of follicular aspiration and flushing on the miscarriage rate. Data suggest little or no difference between follicular flushing and aspiration alone with respect to oocyte yield, total embryo number, or number of cryopreserved embryos. In addition, follicular flushing probably makes little or no difference in the clinical pregnancy rate. Evidence was insufficient to allow any firm conclusions with respect to adverse events or safety.
A new flow-based design for double-lumen needles Cimpeanu, Radu; Castrejón-Pita, Alfonso A.; Lim, Lee Nai ...
Journal of biomechanics,
November 2023, 2023-Nov, 2023-11-00, 20231101, Letnik:
160
Journal Article
Recenzirano
Odprti dostop
Oocyte retrieval forms a crucial part of in vitro fertilisation treatment and its ultimate outcome. Standard double-lumen needles, which include a sequence of aspiration and flushing steps, are ...characterised by a similar success rate to single-lumen needles, despite their increased cost. A novel hydrodynamics-based needle called the OxIVF needle is proposed here, which is geared towards the generation of an internal flow field within the full follicular volume via laterally, rather than frontally, oriented flushing, leading to successful retrievals with no additional stress on the oocyte. A two-dimensional digital twin of the follicular environment is created and tested via multi-phase flow direct numerical simulation. Oocyte initial location within the follicle is varied, while quantities of interest such as velocity magnitude and vorticity are measured with a high level of precision. This provides insight into the overall fluid motion, as well as the trajectory and stresses experienced by the oocyte. A comparative benchmark set of tests indicated a higher success rate of the OxIVF needle of up to 100%, marking a significant improvement over the traditional double-lumen design whose success rate of no more than 75% was also highly dependent on the location of the needle tip inside the follicle. All forces measured during these tests showcase how the oocyte experiences stresses which are no larger than at the aspiration point, with the flow field providing a gentle steering effect towards the extraction region. Finally, the flow generation strategy maximises oocyte yield, unlocking new capabilities in both human and veterinary contexts.
Progesterone is widely used to prolong gestation in women at risk of preterm labour (PTL), and acts at least in part via the inhibition of inflammatory cytokine-induced prostaglandin synthesis. This ...study investigates the mechanisms responsible for this inhibition in human myometrial cells. We used reporter constructs to demonstrate that interleukin 1beta (IL-1β) inhibits progesterone driven PRE activation via p65 activation and that IL-1β reduced progesterone driven gene expression (FKBP5). Conversely, we found that the activity of a p65-driven NFκB reporter construct was reduced by overexpression of progesterone receptor B (PRB) alone and that this was enhanced by the addition of MPA and that both MPA and progesterone suppressed IL-1β-driven cyclo-oxygenase-2 (COX-2) expression. We found that over-expressed Halo-tagged PRB, but not PRA, bound to p65 and that in IL-1β-treated cells, with no overexpression of either PR or p65, activated p65 bound to PR. However, we found that the ability of MPA to repress IL-1β-driven COX-2 expression was not enhanced by overexpression of either PRB or PRA and that although the combined PR and GR antagonist Ru486 blocked the effects of progesterone and MPA, the specific PR antagonist, Org31710, did not, suggesting that progesterone and MPA act via GR and not PR. Knockdown using siRNA confirmed that both MPA and progesterone acted via GR and not PR or AR to repress IL-1β-driven COX-2 expression. We conclude that progesterone acts via GR to repress IL-1β-driven COX-2 activation and that although the interaction between p65 and PRB may be involved in the repression of progesterone driven gene expression it does not seem to be responsible for progesterone repression of IL-1β-induced COX-2 expression.
High throughput sequencing has previously identified differentially expressed genes (DEGs) and enriched signalling networks in human myometrium for term (≥37 weeks) gestation labour, when defined as ...a singular state of activity at comparison to the non-labouring state. However, transcriptome changes that occur during transition from early to established labour (defined as ≤3 and >3 cm cervical dilatation, respectively) and potentially altered by fetal membrane rupture (ROM), when adapting from onset to completion of childbirth, remained to be defined. In the present study, we assessed whether differences for these two clinically observable factors of labour are associated with different myometrial transcriptome profiles. Analysis of our tissue ('bulk') RNA-seq data (NCBI Gene Expression Omnibus: GSE80172) with classification of labour into four groups, each compared to the same non-labour group, identified more DEGs for early than established labour; ROM was the strongest up-regulator of DEGs. We propose that lower DEGs frequency for early labour and/or ROM negative myometrium was attributed to bulk RNA-seq limitations associated with tissue heterogeneity, as well as the possibility that processes other than gene transcription are of more importance at labour onset. Integrative analysis with future data from additional samples, which have at least equivalent refined clinical classification for labour status, and alternative omics approaches will help to explain what truly contributes to transcriptomic changes that are critical for labour onset. Lastly, we identified five DEGs common to all labour groupings; two of which (AREG and PER3) were validated by qPCR and not differentially expressed in placenta and choriodecidua.
Background
Tubal disease accounts for 20% of infertility cases. Hydrosalpinx, caused by distal tubal occlusion leading to fluid accumulation in the tube(s), is a particularly severe form of tubal ...disease negatively affecting the outcomes of assisted reproductive technology (ART). It is thought that tubal surgery may improve the outcome of ART in women with hydrosalpinges.
Objectives
To assess the effectiveness and safety of tubal surgery in women with hydrosalpinges prior to undergoing conventional in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).
Search methods
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, DARE, and two trial registers on 8 January 2020, together with reference checking and contact with study authors and experts in the field to identify additional trials.
Selection criteria
Randomised controlled trials (RCTs) comparing surgical treatment versus no surgical treatment, or comparing surgical interventions head‐to‐head, in women with tubal disease prior to undergoing IVF.
Data collection and analysis
We used Cochrane's standard methodological procedures. The primary outcomes were live birth rate (LBR) and surgical complication rate per woman randomised. Secondary outcomes included clinical, multiple and ectopic pregnancy rates, miscarriage rates and mean numbers of oocytes retrieved and of embryos obtained.
Main results
We included 11 parallel‐design RCTs, involving a total of 1386 participants. The included trials compared different types of tubal surgery (salpingectomy, tubal occlusion or transvaginal aspiration of hydrosalpingeal fluid) to no tubal surgery, or individual interventions to one another. We assessed no studies as being at low risk of bias across all domains, with the main limitations being lack of blinding, wide confidence intervals and low event and sample sizes. We used GRADE methodology to rate the quality of the evidence. Apart from one moderate‐quality result in one review comparison, the evidence provided by these 11 trials ranged between very low‐ to low‐quality.
Salpingectomy versus no tubal surgery
No included study reported on LBR for this comparison. We are uncertain of the effect of salpingectomy on surgical complications such as the rate of conversion to laparotomy (Peto odds ratio (OR) 5.80, 95% confidence interval (CI) 0.11 to 303.69; one RCT; n = 204; very low‐quality evidence) and pelvic infection (Peto OR 5.80, 95% CI 0.11 to 303.69; one RCT; n = 204; very low‐quality evidence). Salpingectomy probably increases clinical pregnancy rate (CPR) versus no surgery (risk ratio (RR) 2.02, 95% CI 1.44 to 2.82; four RCTs; n = 455; I2 = 42.5%; moderate‐quality evidence). This suggests that in women with a CPR of approximately 19% without tubal surgery, the rate with salpingectomy lies between 27% and 52%.
Proximal tubal occlusion versus no surgery
No study reported on LBR and surgical complication rate for this comparison. Tubal occlusion may increase CPR compared to no tubal surgery (RR 3.21, 95% CI 1.72 to 5.99; two RCTs; n = 209; I2 = 0%; low‐quality evidence). This suggests that with a CPR of approximately 12% without tubal surgery, the rate with tubal occlusion lies between 21% and 74%.
Transvaginal aspiration of hydrosalpingeal fluid versus no surgery
No study reported on LBR for this comparison, and there was insufficient evidence to identify a difference in surgical complication rate between groups (Peto OR not estimable; one RCT; n = 176). We are uncertain whether transvaginal aspiration of hydrosalpingeal fluid increases CPR compared to no tubal surgery (RR 1.67, 95% CI 1.10 to 2.55; three RCTs; n = 311; I2 = 0%; very low‐quality evidence).
Laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy
We are uncertain of the effect of laparoscopic proximal tubal occlusion versus laparoscopic salpingectomy on LBR (RR 1.21, 95% CI 0.76 to 1.95; one RCT; n = 165; very low‐quality evidence) and CPR (RR 0.81, 95% CI 0.62 to 1.07; three RCTs; n = 347; I2 = 77%; very low‐quality evidence). No study reported on surgical complication rate for this comparison.
Transvaginal aspiration of hydrosalpingeal fluid versus laparoscopic salpingectomy
No study reported on LBR for this comparison, and there was insufficient evidence to identify a difference in surgical complication rate between groups (Peto OR not estimable; one RCT; n = 160). We are uncertain of the effect of transvaginal aspiration of hydrosalpingeal fluid versus laparoscopic salpingectomy on CPR (RR 0.69, 95% CI 0.44 to 1.07; one RCT; n = 160; very low‐quality evidence).
Authors' conclusions
We found moderate‐quality evidence that salpingectomy prior to ART probably increases the CPR compared to no surgery in women with hydrosalpinges. When comparing tubal occlusion to no intervention, we found that tubal occlusion may increase CPR, although the evidence was of low quality. We found insufficient evidence of any effect on procedure‐ or pregnancy‐related adverse events when comparing tubal surgery to no intervention. Importantly, none of the studies reported on long term fertility outcomes. Further high‐quality trials are required to definitely determine the impact of tubal surgery on IVF and pregnancy outcomes of women with hydrosalpinges, particularly for LBR and surgical complications; and to investigate the relative efficacy and safety of the different surgical modalities in the treatment of hydrosalpinges prior to ART.
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