Timed intercourse for couples trying to conceive.

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.

Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery.

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, abstracts 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).

Surgical interventions for the management of chronic pelvic pain in women.

BACKGROUND: Chronic pelvic pain (CPP) is a common gynaecological condition accounting for 20% of all gynaecological referrals. There are wide ranges of causes with overlapping symptomatology, therefore the management of the condition is a formidable challenge for clinicians. The aetiology of CPP is heterogeneous and in many cases, no clear diagnosis can be reached. It is in this scenario that the label of chronic pelvic pain syndrome (CPPS) can be applied. We defined women with CPPS as having a minimum duration of pain of at least 6 months, including with a diagnosis of pelvic congestion syndrome, but excluding pain caused by a condition such as endometriosis. Many surgical interventions have been tried in isolation or in conjunction with non-surgical interventions in the management with variable results. Surgical interventions are invasive and carry operative risks. Surgical interventions must be evaluated for their effectiveness prior to their prevalent use in the management of women with CPPS. OBJECTIVES: To review the effectiveness and safety of surgical interventions in the management of women with CPPS. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register of Controlled Trials, CENTRAL, MEDLINE, Embase and PsycINFO, on 23 April 2021 for any randomised controlled trials (RCT) for surgical interventions in women with CPPS. We also searched the citation lists of relevant publications, two trial registries, relevant journals, abstracts, conference proceedings and several key grey literature sources. SELECTION CRITERIA: RCTs with women who had CPPS. The review authors were prepared to consider studies of any surgical intervention used for the management of CPPS. Outcome measures were pain rating scales, adverse events, psychological outcomes, quality of life (QoL) measures and requirement for analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies for inclusion and extracted data using the forms designed according to Cochrane guidelines. For each included trial, we collected information regarding the method of randomisation, allocation concealment, blinding, data reporting and analyses. We reported pooled results as mean difference (MDs) or odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. If similar outcomes were reported on different scales, we calculated the standardised mean difference (SMD). We applied GRADE criteria to judge the overall certainty of the evidence. MAIN RESULTS: Four studies met our inclusion criteria involving 216 women with CPP and no identifiable cause. Adhesiolysis compared to no surgery or diagnostic laparoscopy We are uncertain of the effect of adhesiolysis on pelvic pain scores postoperatively at three months (MD -7.3, 95% CI -29.9 to 15.3; 1 study, 43 participants; low-certainty evidence), six months (MD -14.3, 95% CI -35.9 to 7.3; 1 study, 43 participants; low-certainty evidence) and 12 months postsurgery (MD 0.00, 95% CI -4.60; 1 study, 43 participants; very low-certainty evidence). Adhesiolysis may improve both the emotional wellbeing (MD 24.90, 95% CI 7.92 to 41.88; 1 study, 43 participants; low-certainty evidence) and social support (MD 23.90, 95% CI -1.77 to 49.57; 1 study, 43 participants; low-certainty evidence) components of the Endometriosis Health Profile-30, and both the emotional component (MD 32.30, 95% CI 13.16 to 51.44; 1 study, 43 participants; low-certainty evidence) and the physical component of the 12-item Short Form (MD 22.90, 95% CI 10.97 to 34.83; 1 study, 43 participants; low-certainty evidence) when compared to diagnostic laparoscopy. We are uncertain of the safety of adhesiolysis compared to comparator groups due to low-certainty evidence and lack of structured adverse event reporting. No studies reported on psychological outcomes or requirements for analgesia. Laparoscopic uterosacral ligament ablation or resection compared to diagnostic laparoscopy/other treatment We are uncertain of the effect of laparoscopic uterosacral ligament/nerve ablation (LUNA) or resection compared to other treatments postoperatively at three months (OR 1.26, 95% CI 0.40 to 3.93; 1 study, 51 participants; low-certainty evidence) and six months (MD -2.10, 95% CI -4.38 to 0.18; 1 study, 74 participants; very low-certainty evidence). At 12 months post-surgery, we are uncertain of the effect of LUNA on the rate of successful treatment compared to diagnostic laparoscopy. One study of 56 participants found no difference in the effect of LUNA on non-cyclical pain (P = 0.854) or dyspareunia (P = 0.41); however, there was a difference favouring LUNA on dysmenorrhea (P = 0.045) and dyschezia (P = 0.05). We are also uncertain of the effect of LUNA compared to vaginal uterosacral ligament resection on pelvic pain at 12 months (MD 2.00, 95% CI 0.47 to 3.53; 1 study, 74 participants; very low-certainty evidence). We are uncertain of the safety of LUNA or resection compared to comparator groups due to the lack of structured adverse event reporting. Women undergoing LUNA may require more analgesia postoperatively than those undergoing other treatments (P < 0.001; 1 study, 74 participants). No studies reported psychological outcomes or QoL. AUTHORS' CONCLUSIONS: We are uncertain about the benefit of adhesiolysis or LUNA in management of pain in women with CPPS based on the current literature. There may be a QoL benefit to adhesiolysis in improving both emotional wellbeing and social support, as measured by the validated QoL tools. It was not possible to synthesis evidence on adverse events as these were only reported narratively in some studies, in which none were observed. With the inadequate objective assessment of adverse events, especially long-term adverse events, associated with adhesiolysis or LUNA for CPPS, there is currently little to support these interventions for CPPS.

When to Do Surgery and When Not to Do Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis with the aim to answer whether operative laparoscopy is an effective treatment in a woman with demonstrated endometriosis compared with alternative treatments. Moreover, we aimed to assess the risks of operative laparoscopy compared with those of alternatives. In addition, we aimed to systematically review the literature on the impact of patient preference on decision making around surgery. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, ClinicalTrials.gov, CINAHL, Scopus, OpenGrey, and Web of Science from inception through May 2019. In addition, a manual search of reference lists of relevant studies was conducted. METHODS OF STUDY SELECTION: Published and unpublished randomized controlled trials (RCTs) in any language describing a comparison between surgery and any other intervention were included, with particular reference to timing and its impact on pain and fertility. Studies reporting on keywords including, but not limited to, endometriosis, laparoscopy, pelvic pain, and infertility were included. In the anticipated absence of RCTs on patient preference, all original research on this topic was considered eligible. TABULATION, INTEGRATION, AND RESULTS: In total, 1990 studies were reviewed. Twelve studies were identified as being eligible for inclusion to assess outcomes of pain (n = 6), fertility (n = 7), quality of life (n = 1), and disease progression (n = 3). Seven studies of interest were identified to evaluate patient preferences. There is evidence that operative laparoscopy may improve overall pain levels at 6 months compared with diagnostic laparoscopy (risk ratio [RR], 2.65; 95% confidence interval [CI], 1.61-4.34; p <.001; 2 RCTs, 102 participants; low-quality evidence). Because the quality of the evidence was very low, it is uncertain if operative laparoscopy improves live birth rates. Operative laparoscopy probably yields little or no difference regarding clinical pregnancy rates compared with diagnostic laparoscopy (RR, 1.29; 95% CI, 0.99-1.92; p = .06; 4 RCTs, 624 participants; moderate-quality evidence). It is uncertain if operative laparoscopy yields a difference in adverse outcomes when compared with diagnostic laparoscopy (RR, 1.98; 95% CI, 0.84-4.65; p = .12; 5 RCTs, 554 participants; very-low-quality evidence). No studies reported on the progression of endometriosis to a symptomatic state or progression of extent of disease in terms of volume of lesions and locations in asymptomatic women with endometriosis. We found no studies that reported on the timing of surgery. No quantitative or qualitative studies specifically aimed at elucidating the factors informing a woman's choice for surgery were identified. CONCLUSION: Operative laparoscopy may improve overall pain levels but may have little or no difference with respect to fertility-related or adverse outcomes when compared with diagnostic laparoscopy. Additional high-quality RCTs, including comparing surgery to medical management, are needed, and these should report adverse events as an outcome. Studies on patient preference in surgical decision making are needed (International Prospective Register of Systematic Review registration number: CRD42019135167).

Safety, biodistribution and radiation dosimetry of the Arg-Gly-Asp peptide 99m Tc-maraciclatide in healthy volunteers.

BACKGROUND: 99m Tc-Maraciclatide is a radiolabelled RGD (Arg-Gly-Asp) peptide that binds with high affinity to α v ß 3 and α v ß 5 integrins, common receptors upregulated in disease states involving angiogenesis and inflammation. As such, it holds promise as a novel diagnostic imaging agent for a range of pathological conditions. The present study provides the safety, biodistribution and radiation dosimetry of 99m Tc-maraciclatide in healthy volunteers. METHODS: A phase 1, randomised, placebo-controlled study assessed the safety, biodistribution and radiation dosimetry of 99m Tc-maraciclatide in healthy volunteers. Participants were randomised into three groups receiving 99m Tc-maraciclatide and three chemical amounts of maraciclatide in an escalating dose protocol. Eight participants in each group received the required amount of maraciclatide via intravenous injection, with the remaining two receiving a placebo. Biodistribution was assessed by acquiring scintigraphic images at time points up to 24 h after a bolus injection of 99m Tc-maraciclatide. 99m Tc-maraciclatide activity in plasma and urine was measured up to 7 days post-administration. RESULTS: 99m Tc-maraciclatide was safe and well tolerated, with no serious adverse events reported. Initial uptakes of 99m Tc were highest in the gastrointestinal tract (20%), liver (15%), and lungs (9%). Similarly, the regions with the highest normalised cumulated activities were the contents of the urinary bladder and voided urine (3.4 ±â€…0.4 MBq*h/MBq), the combined walls of the small intestine and upper and lower large intestine (0.9 ±â€…0.2 MBq*h/MBq), liver (0.8 ±â€…0.2 MBq*h/MBq), lung (0.4 ±â€…0.1 MBq*h/MBq). The main route of 99m Tc excretion was renal (55%), with a systemic urinary clearance of approximately 6.7 ml/min/kg. The pharmacokinetic analysis gave a mean apparent terminal elimination half-life of the unlabelled molecular maraciclatide of approximately 1 h, independent of dose. The mean ED per unit injected activity was 7.8 ±â€…0.8 µSv/MBq. CONCLUSION: 99m Tc-maraciclatide is a safe radiopharmaceutical formulation with a dosimetry profile similar to other 99m Tc-based imaging agents.

Crimson clues: advancing endometriosis detection and management with novel blood biomarkers.

Endometriosis is an inflammatory condition affecting approximately 10% of the female-born population. Despite its prevalence, the lack of noninvasive biomarkers has contributed to an established global diagnostic delay. The intricate pathophysiology of this enigmatic disease may leave signatures in the blood, which, when detected, can be used as noninvasive biomarkers. This review provides an update on how investigators are utilizing the established disease pathways and innovative methodologies, including genome-wide association studies, next-generation sequencing, and machine learning, to unravel the clues left in the blood to develop blood biomarkers. Many blood biomarkers show promise in the discovery phase, but because of a lack of standardized and robust methodologies, they rarely progress to the development stages. However, we are now seeing biomarkers being validated with high diagnostic accuracy and improvements in standardization protocols, providing promise for the future of endometriosis blood biomarkers.

The effect of oil pulling with coconut oil to improve dental hygiene and oral health: A systematic review.

OBJECTIVES: Coconut oil is a cheap and accessible oil for many people around the world. There are numerous advocates for the practice of oil pulling to prevent common oral diseases. Therefore determining the effectiveness of oil pulling with coconut oil could potentially have monumental benefits. This review aimed to assess the effect of oil pulling with coconut oil in improving oral health and dental hygiene. DATA: We included randomized controlled trials comparing the effect of oil pulling with coconut oil on improving oral health and dental hygiene.No meta-analysis was performed due to the clinical heterogeneity and differences in the reporting of data among the included studies. SOURCES: Six electronic databases were screened: PubMed, Medline, EMBASE, AMED, CENTRAL and CINAHL. STUDY SELECTION: Electronic searches yielded 42 eligible studies, of which four RCTs including 182 participants were included. The studies lasted between 7 and 14 days. Significant differences were demonstrated for a reduction in salivary bacterial colony count (p = 0.03) and plaque index score (p=<0.001). One study also demonstrated a significant difference in staining compared to using Chlorhexidine (p = 0.0002). However, data was insufficient for conclusive findings, the quality of studies was mixed and risk of bias was high. CONCLUSION: The limited evidence suggests that oil pulling with coconut oil may have a beneficial effect on improving oral health and dental hygiene. Future clinical trials are of merit considering the universal availability of the intervention. Prospective research should have a robust design with rigorous execution to provide a higher quality of evidence. CLINICAL SIGNIFICANCE: Oil pulling with coconut oil could be used as a adjunct to normal preventative regimes to improve oral health and dental hygiene although further studies are needed to determine the level of effectiveness.