Protocol For Women Research Articles

Fixed versus flexible gonadotropin releasing hormone antagonist protocol in women with polycystic ovary syndrome undergoing in vitro fertilization: An RCT.

Despite the extensive use of the gonadotropin-releasing hormone (GnRH) antagonist protocol in treating infertile women, particularly those with polycystic ovary syndrome (PCOS), there have not been sufficient evidence to compare the flexible and fixed variants in in vitro fertilization (IVF) cycles. This study aims to assess the treatment outcomes of flexible and fixed types of GnRH-antagonist protocol for IVF in women with PCOS. In this randomized clinical trial, 150 infertile women with PCOS, who were candidates for IVF, and referred to the Yazd Research and Clinical Center for Infertility, Yazd, Iran between October 2023 and February 2024 were included. Participants were divided into 2 groups (n = 75/each) based on the type of antagonist protocol (fixed or flexible). GnRH antagonist administration started on the 5 day of gonadotropin treatment in the fixed group. In the flexible group when there was at least one follicle 12-14 mm, GnRH antagonist was started. Finally, the number of metaphase II oocyte, the quality of embryos, the duration of the stimulation cycle, the dose of gonadotropin, the number of GnRH-antagonist, and the rate of ovarian hyperstimulation syndrome were evaluated. No statistically significant difference was observed in terms of cycle length and the total dose of gonadotropin between groups. Nevertheless, a notable distinction was observed in the total number of oocytes (17.84 vs. 15.5, p = 0.023) and mature oocytes (13.64 vs. 11.83, p = 0.019) in the flexible group compared to the fixed group. In conclusion, the IVF outcomes are more favorable in women with PCOS undergoing the flexible GnRH-antagonist protocol compared to the fixed protocol.

Lactation induction: a protocol for women with endocrine conditions, surrogate mothers and same-sex couples

Lactation induction: a protocol for women with endocrine conditions, surrogate mothers and same-sex couples

Cost-Effectiveness of Clomiphene Citrate-Based Minimal Stimulation Compared with Controlled Ovarian Stimulation Protocol in Women with Diminished Ovarian Reserve

Background: In Japan, where infertility treatment is now covered by insurance, appropriate protocols for patients with diminished ovarian reserve (DOR) based on treatment outcomes and cost-effectiveness must be selected. Therefore, this study aims to provide information on the outcomes and cost-effectiveness of conventional ovarian stimulation and mild stimulation for patients with DOR in Japan. Methods: Data from 66 women who underwent first oocyte retrieval at Showa University Hospital between May 2019 and November 2023 were analyzed. Results: The clomiphene citrate (CC) group used significantly fewer gonadotropins and incurred lower costs than the conventional ovarian stimulation group while achieving comparable clinical outcomes, including cumulative live birth rates. Conclusions: CC-based minimal stimulation is a cost-effective alternative to conventional ovarian stimulation for patients with low ovarian reserve without compromising clinical efficacy. Further randomized controlled trials are required to confirm these findings and optimize protocols for this population.

Maternal and perinatal infectious morbidity in term prelabor rupture of membrane according to two induction of labor protocols.

The optimal labor-induction protocol in women with prelabor rupture of membranes (PROM) is unknown. Whether the management of women with a previous cesarean delivery (CD) with PROM is different remains controversial. We investigated maternal and perinatal outcomes according to two induction protocols of 24h vs. 12h. In July 2021, our protocol of induction of labor in term-PROM was extended from 12h to 24h post-PROM. We compared obstetrical and neonatal outcomes before and after the change. A subgroup analysis of women with previous CD was performed. Results were compared using a univariate analysis. A multivariable model was described to predict neonatal intensive care unit admission (NICU) and clinical chorioamnionitis. The 24h and 12h ROM-to-induction protocol groups included 962 and 802 women, respectively. In the 24h group, a higher proportion of women labored spontaneously (p < 0.001), the rate of chorioamnionitis was higher (p = 0.017), and the CD rate was similar. Admission to the NICU (p = 0.012), antibiotic administration (p = 0.003), and respiratory distress (p = 0.002) were also greater in the 24h induction group. Among women with a history of CD (n = 143), the need for oxytocin (p = 0.003) and delivery by CD (p = 0.016) were lower in the 24 vs. 12h group. Our results advocate shared decision-making in the expectant management of term-PROM. Women should be informed of the lower chance for induction and the higher risk of infections and neonatal complications with a 24-h induction approach. Longer expectant management in women with a previous CD resulted in significantly lower induction and CD rates.

P-577 A randomized trial to compare the live birth rate following the progestin-primed ovarian stimulation versus the antagonist protocol in women with anticipated high ovarian responses

Abstract Study question Is there difference in the live birth rate following the progestin-primed ovarian stimulation (PPOS) versus the antagonist protocol in women with anticipated high ovarian responses? Summary answer The live birth rates of the first frozen embryo transfer following PPOS and the antagonist protocol were comparable in women with anticipated high ovarian responses. What is known already Progestin when given orally inhibits the pituitary LH surge during ovarian stimulation when taken orally i.e. progestin-primed ovarian stimulation. Two randomized trials showed similar number of oocytes for PPOS and the antagonist protocol in oocyte donation cycles. However, there is still no randomized trial to compare the live birth rate between PPOS and the antagonist protocol. Study design, size, duration This is a randomized controlled trial of 784 infertile women conducted from June 2020 and October 2021. Participants/materials, setting, methods Infertile women aged &amp;lt;43 years undergoing the first IVF cycle in a tertiary fertility center and having antral follicle count &amp;gt;15 randomly assigned in a 1:1 ratio into two groups: PPOS group and the antagonist group. Medroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the PPOS group. The primary outcome was the live birth rate of the first frozen embryo transfer. Main results and the role of chance 784 women were randomly assigned into two groups: PPOS group (n = 392) and antagonist group (n = 392). Embryo transfer was either cancelled or postponed in 62 (62/392, 15.8%) women in the PPOS group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no frozen embryo transfer within 6 months following randomization. The two groups were similar in demographic characteristics and number of oocytes obtained/fertilized, the number of cleaving embryos, number of good quality embryos at day 3, number of blastocysts developed and number of embryo/blastocyst frozen. There was no statistically significant difference in the live birth rate of the first frozen embryo transfer cycle between the progestin-primed ovarian stimulation and antagonist groups based on both intention to treat [37.5.0% (147/392) versus 32.7% (128/392), RR 1.148 (95% CI = 0.949–1.390), P = 0.16] and per protocol analysis [44.5% (147/330) versus 39.1.% (128/327), RR 1.138 (95%CI = 0.950–1.364), P = 0.16]. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and cumulative live birth rates. Limitations, reasons for caution Women with anticipated high ovarian responses were recruited and the results may not be extrapolated to the general population seeking IVF. This is not a blind study although the live birth rate as the primary outcome is objection. The duration of the study is 6 months since randomization. Wider implications of the findings In situations in which fresh embryo transfer is not required such as oocyte/embryo freezing for fertility preservation, oocyte donation or preimplantation genetic testing, the PPOS protocol may be preferred over the antagonist protocol. Trial registration number NCT04414761

The cumulative live birth rate and cost-effectiveness of the clomiphene and gonadotropin cotreatment protocol versus the mid-luteal GnRH agonist protocol in women over 35 years old

The decrease in assisted reproductive technology success among older women, attributed to decreased oocyte quantity and quality, poses a significant challenge. Currently, no consensus on the optimal ovarian stimulation protocol for older women undergoing IVF exists. This retrospectively registered cohort study aimed to compare the cumulative live birth rate (CLBR), time to live birth (TTLB), and cost-effectiveness among women older than 35 years who were receiving either the gonadotropin-releasing hormone agonist (GnRHa) or clomiphene citrate and gonadotropin cotreatment with ovarian stimulation (CC cotreatment) protocol. To compare treatment outcomes, we performed propensity score matching (PSM) on 2871 IVF cycles in women older than 35 years who received either the GnRHa or CC cotreatment protocol, resulting in 375 cycles in each group. Additionally, a decision tree model was utilized to assess the cost-effectiveness of the two protocols. Following PSM, both groups had similar baseline characteristics. The CC cotreatment protocol resulted in a greater rate of cycle cancellation (13.07% vs. 8.00%, p = 0.032), but the groups maintained comparable fertilization rates and embryo quality. Although the TTLB was longer in the CC cotreatment group, the CLBR per initial cycle (41.07% vs. 45.33%, p = 0.269) and delivery outcomes were similar between the two groups at the 24 months follow-up. Additionally, the average cost per live birth in the CC cotreatment group was 21.27% lower than in the GnRHa group (¥32,301.42 vs. ¥39,174.22). In conclusion, for women older than 35 years undergoing IVF, the CC cotreatment protocol offered a comparable CLBR to the GnRHa protocol but with reduced costs, indicating its potential as a viable and cost-effective ovarian stimulation option.Clinical trial registration: https://www.chictr.org.cn/, identifier [ChiCTR2300076537].

Comparing blastocyst euploid rates between the progestin-primed and gonadotrophin-releasing hormone antagonist protocols in aneuploidy genetic testing: a randomised trial protocol

IntroductionProgestin can inhibit the pituitary luteinising hormone (LH) surge during ovarian stimulation for in vitro fertilisation (IVF) and studies show progestin-primed ovarian stimulation (PPOS) is effective in blocking the LH...

Letrozole cotreatment progestin-primed ovarian stimulation in women undergoing controlled ovarian stimulation for in vitro fertilization.

To investigate the impact of letrozole cotreatment progestin-primed ovarian stimulation (PPOS) (Le PPOS) in controlled ovarian stimulation (COS) and the pregnancy outcomes in frozen-thawed embryo transfer cycles. This retrospective cohort study included women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). A total of 2575 cycles were included (1675 in the Le PPOS group and 900 in the PPOS group). The primary outcome was the clinical pregnancy rates. The secondary outcome was the live birth rates. In this study, propensity score matching (PSM) was performed to create a perfect match of 379 patients in each group. After matching, the numbers of oocytes retrieved, mature oocytes, fertilization, and clinical pregnancy rates were more favorable in the Le PPOS group than in the PPOS group (all p < 0.05). The multivariable analysis showed that the clinical pregnancy rate was higher in the Le PPOS than in the PPOS group (odds ratio = 1.46, 95% confidence interval: 1.05-2.04, p = 0.024) after adjusting for potentially confounding factors (age, anti-Müllerian hormone levels, antral follicular count, the type of embryo transferred, number of transferred embryos, body mass index, and follicular stimulating hormone and estradiol levels on starting day). This retrospective study with a limited sample size suggests that the Le PPOS protocol might be an alternative to the PPOS protocol in women undergoing COS and could lead to better pregnancy outcomes. The results should be confirmed using a formal randomized controlled trial.

A randomized controlled trial to compare the live birth rate of the first frozen embryo transfer following the progestin-primed ovarian stimulation protocol vs. the antagonist protocol in women with an anticipated high ovarian response

ObjectiveTo compare the live birth rate of the first frozen embryo transfer following ovarian stimulation by the progestin-primed ovarian stimulation protocol versus the antagonist protocol in women with anticipated high ovarian response undergoing IVF DesignRandomized controlled trial SettingsA tertiary assisted reproduction center PatientsInfertile women aged <43 years undergoing the first IVF cycle and having antral follicle count >15 InterventionsMedroxyprogesterone 10 mg daily was given from the start of ovarian stimulation until the day of ovulation trigger in the progestin-primed ovarian stimulation protocol. In the antagonist protocol, an antagonist 0.25mg daily was given from 6th day of ovarian stimulation until the day of ovulation trigger. Blinding was not possible for women or physicians but the biostatistician was blinded to the group assignment. Main Outcome MeasuresLive birth rate of the first frozen embryo transfer cycle Results784 women were recruited from June 2020 and October 2021 and randomly assigned in a 1:1 ratio into two groups: progestin-primed ovarian stimulation group (n=392) and antagonist group (n=392). Embryo transfer was either cancelled or postponed in 62 (62/392, 15.8%) women in the progestin-primed ovarian stimulation group and 65 (65/392, 16.6%) in the antagonist group because of no transferable embryos or no frozen embryo transfer within 6 months following randomizaion. The two groups were similar in demographic characteristics and number of oocytes obtained/fertilized, the number of cleaving embryos, number of good quality embryos at day 3, number of blastocysts developed and number of embryo/blastocyst frozen. There was no statistically significant difference in the live birth rate of the first frozen embryo transfer cycle between the progestin-primed ovarian stimulation and antagonist groups based on both intention to treat [37.5.0% (147/392) versus 32.7% (128/392), RR 1.148 (95% CI=0.949–1.390), P=0.16] and per protocol analysis [44.5% (147/330) versus 39.1.% (128/327), RR 1.138 (95%CI = 0.950–1.364), P=0.16]. Both groups showed comparable clinical pregnancy, ongoing pregnancy, miscarriage, multiple pregnancy, ectopic pregnancy and cumulative live birth rates. ConclusionThe live birth rates of the first frozen embryo transfer following the progestin-primed ovarian stimulation and the antagonist protocol were comparable in women with an anticipated high ovarian response.

Dynamic serum testosterone concentration may predict in vitro fertilization yield during ovarian stimulation by a gonadotrophin‐releasing hormone agonist long protocol in women with normal ovarian reserve

AbstractObjectiveTo determine whether dynamic changes in serum total testosterone (TT) levels during controlled ovarian stimulation (COS) by a GnRH‐a (gonadotrophin‐releasing hormone agonist) long protocol may predict pregnancy in women with normal ovarian reserve in in vitro fertilization.MethodsThe TT measurements were added to routine hormone tests during COS. The TT dynamic changes, clinical pregnancy rate, and quality of oocytes and embryos of 109 patients were analyzed.ResultsCompared with the non‐pregnancy group, in the pregnancy group the TT level on Gn initial day (TTinitial‐d) increased sharply when the dominant follicle reached a diameter 10–12 mm [TTfΦ (10–12)‐d] and on human chorionic gonadotrophin (HCG) day (TTHCG‐d), also the ratios of TTfΦ (10–12)‐d to TTinitial‐d (1.23 ± 0.37 vs. 1.10 ± 0.58, p = 0.040) and TTHCG‐d to TTinitial‐d (2.32 ± 1.26 vs. 2.00 ± 1.43, p = 0.019) increased notably. Of the 2 TT ratios, the first tertile limit was regarded as the threshold of high TT ratios (1.00, 1.45). High tertiles had higher pregnancy rates than low tertiles (82.86% vs. 42.11%, p = 0.006; 71.43% vs. 44.83%, p = 0.040). The 2 TT ratios were positively associated with the number of metaphase II oocytes and good‐quality embryos.ConclusionOf COS in a long GnRH‐a protocol with optimized outcome, serum TT kinetics appears to be characterized by sharp rises at the early and late stages of follicle growth. The ratios of TTΦ (10–12)‐d to TTinitial‐d and TTHCG‐d to TTinitial‐d may be predictors for pregnancy and qualitative outcomes of oocytes and embryos.

Safety and efficacy of a four-step outpatient platinum desensitization protocol in women with gynecologic cancers who have had a platinum hypersensitivity reaction (2220)

Safety and efficacy of a four-step outpatient platinum desensitization protocol in women with gynecologic cancers who have had a platinum hypersensitivity reaction (2220)

High-Temporal/High-Spatial Resolution Breast Magnetic Resonance Imaging Improves Diagnostic Accuracy Compared With Standard Breast Magnetic Resonance Imaging in Patients With High Background Parenchymal Enhancement.

To compare breast magnetic resonance imaging (MRI) diagnostic performance using a standard high-spatial resolution protocol versus a simultaneous high-temporal/high-spatial resolution (HTHS) protocol in women with high levels of background parenchymal enhancement (BPE). We conducted a retrospective study of contrast-enhanced breast MRIs performed at our institution before and after the introduction of the HTHS protocol. We compared diagnostic performance of the HTHS and standard protocol by comparing cancer detection rate (CDR) and positive predictive value of biopsy (PPV3) among women with high BPE (ie, marked or moderate). Among women with high BPE, the HTHS protocol demonstrated increased CDR (23.6 per 1,000 patients v 7.9 per 1,000 patients; P = 0. 013) and increased PPV3 (16.0% v 6.3%; P = .021) compared with the standard protocol. This corresponded to a 9.8% (95% CI, 1.29 to 18.3) decrease in the proportion of unnecessary biopsies among high-BPE patients and an additional cancer yield of 15.7 per 1,000 patients (95% CI, 1.3 to 18.3). Among women with high BPE, HTHS MRI improved diagnostic performance, leading to an additional cancer yield of 15.7 cancers per 1,000 women and concomitantly decreasing unnecessary biopsies by 9.8%. A multisite prospective trial is warranted to confirm these findings and to pave the way for more widespread clinical implementation.

O-131 BEYOND: a randomised controlled trial comparing efficacy and safety of individualised follitropin delta dosing in GnRH agonist versus antagonist protocols for first ovarian stimulation cycle

Abstract Study question How does a long GnRH agonist versus a GnRH antagonist protocol affect ovarian response when using individualised fixed daily follitropin delta dose for ovarian stimulation? Summary answer BEYOND trial data demonstrates that individualised follitropin delta dosing is safe and effective in a long GnRH agonist protocol in women with AMH ≤35 pmol/L. What is known already Efficacy and safety of a fixed daily dose of follitropin delta, individualised based on bodyweight and anti-Müllerian (AMH), have been established in RCTs using a GnRH antagonist protocol. Preliminary study data shows that individualised follitropin delta is efficacious when used with a long GnRH agonist protocol (RAINBOW trial). There is no comparative data for efficacy and safety of individualised follitropin delta in a long GnRH agonist versus an antagonist protocol. Study design, size, duration This was a randomised, controlled, open-label, multi-centre trial comparing efficacy and safety of individualised follitropin delta dosing in a long GnRH agonist versus an antagonist protocol in participants undergoing their first ovarian stimulation for IVF/ICSI conducted between May 2019 and February 2022. The primary endpoint was the number of oocytes retrieved. Important secondary endpoints included ongoing pregnancy rates and adverse drug reactions, with a special focus on OHSS. A total of 437 participants were randomised. Participants/materials, setting, methods Participants, 18–40 years old with AMH ≤35 pmol/L, were enrolled at specialist reproductive health clinics in Austria, Denmark, Israel, Italy, the Netherlands, Norway and Switzerland. The mean number of oocytes retrieved was compared between the agonist and antagonist protocols using a negative binomial regression model with age and AMH at screening as factors. The analyses were based on all randomised subjects, using a multiple imputation method for randomised subjects withdrawing before start of stimulation. Main results and the role of chance Of the 437 randomised subjects, 202 and 204 initiated ovarian stimulation with follitropin delta in the agonist and antagonist groups, respectively. Baseline mean data were: age, 32.3±4.3 years; AMH, 16.6±7.8 pmol/L, respectively. The number of oocytes retrieved was statistically significantly higher in the agonist (11.1±5.9) versus antagonist (9.6±5.5) group, with an estimated mean difference of 1.31 oocytes (95% CI: 0.22; 2.40, p = 0.0185). The difference in number of oocytes retrieved was influenced by the patients’ age and ovarian reserve, with a greater difference observed in patients &amp;lt;35 years and patients with high ovarian reserve (AMH &amp;gt;15 pmol/L). Cycle cancellations (2.0% versus 3.4%) and transfer cancellations (13.7% versus 14.7%) were similar in both groups. Ongoing pregnancy rate (36.9% vs 29.1%; estimated difference: 7.74% [95% CI: –1.49; 16.97, p = 0.1002]) and other pregnancy outcomes were higher in the agonist versus antagonist protocol group, but the differences were not statistically significant. The most commonly reported adverse events (≥1% in either group) were similar in both groups (headache, OHSS, nausea, pelvic pain or discomfort, and abdominal pain). Incidence of early moderate/severe OHSS was low (1.5% versus 2.5%). Early pregnancy loss was similar between the groups (20% vs 24% of subjects with positive beta-hCG test, respectively). Limitations, reasons for caution Subjects with AMH &amp;gt;35 pmol/L were not enrolled. Clinicians should remain cautious when using a GnRH agonist protocol in patients with AMH &amp;gt;35 pmol/L (greater OHSS risk). OHSS incidence in the GnRH antagonist group may have been lower if a GnRH agonist trigger had been allowed. Wider implications of the findings In women with AMH ≤35 pmol/L, a fixed daily dose of follitropin delta (individualised according to bodyweight and AMH) showed similar efficacy when used in a long GnRH agonist protocol with no additional safety signals observed and no additional risk of OHSS versus follitropin delta used in an antagonist protocol. Trial registration number ClinicalTrials.gov identifier: NCT03809429; EudraCT number: 2017-002783-40

(055) Application of a Very Low Calorie Ketogenic Diet (VLCKD) Protocol in Women's Endocrinology: Psychosexual Correlates of Weight Loss

Abstract Introduction The role of obesity in female sexuality is controversial and there are no intervention studies aimed at evaluating the effect of the Very Low Calories Ketogenic Diet (VLCKD) on female sexual function, in particular on arousal. Objective To evaluate the psychosexual correlates of obesity and Metabolic Syndrome (MetS) in a sample of women consulting for sexual symptoms; to investigate the change in measures of arousal after weight loss obtained with VLCKD. Methods In a retrospective study, n=322 women consulting for sexual symptoms were enrolled. The patients underwent a clinical, laboratory, sexual and psychological examination and were studied by color-Doppler ultrasound for the evaluation of genital vascularization, with measurement of the Pulsatility Index (PI) of the clitoral artery. They completed the Female Sexual Function Index (FSFI), Female Sexual Distress Scale - Revised (FSDS-R), Body Uneasiness Test, Eating Disorder Examination Questionnaire (EDE Q), and Middlesex Hospital Questionnaire, for psychiatric symptoms. Twelve patients underwent a nutritional intervention aimed at weight loss, based on a VLCKD protocol. These cases were compared with patients treated with different strategies for sexual symptoms, in a 1:1 case-control study (matched for BMI, age and menopausal status). Results In the total sample, clitoral PI was significantly higher in obese women (p = 0.018) and in those diagnosed with MetS (p=0.043). A statistically significant inverse correlation emerged between WC ≥ 88 cm and FSFI Arousal score (p=0.028). In patients undergoing a nutritional intervention with VCLKD protocol (n=12), after a mean follow-up of 20+-2 weeks, BMI showed a reduction of 6.7+-2.8 kg/m2 (p&amp;lt;0.001) and WC of 14.3+-5.2 cm (p&amp;lt;0.001), with fat mass loss of 14.6+-5.4 kg (-37.1%; p&amp;lt;0.001). At follow-up, the total FSFI and FSDS-R scores significantly improved (17.0+-13.6 vs. 11.2+-7.9, p=0.016, and 7.4+-8.3 vs. 13.3+-10.6, p=0.039, respectively). Among the FSFI subdomains, Arousal showed a significant increase (p=0.035). We also observed an improvement in EDE total score (p=0.032), Shape (p=0.008) and Weight subscales (p=0.011), BUT-B Positive Symptoms Distress Index (p=0.009) and BUT-A Body Image Concerns (p=0.043), and MHQ total score (p&amp;lt;0.001). The clitoral artery PI at follow-up showed a non-significant reduction. At multivariate analysis, the change in the Total FSFI was correlated with the BUT-B PSDI score change (p=0.031) and the EDE Shape change (p=0.043), when including DeltaMHQ and DeltaWC as further covariates. Finally, in a 1:1 case-control study, a significant difference emerged in the improvement of FSFI total score, which was more relevant in cases than in controls (p=0.046); on the other hand, there was no difference in the change in FSDS-R score between cases and controls. Conclusions Our data suggest that weight loss obtained by VLCKD is associated with an improvement in sexual function, and in particular in Arousal, whose change could be mediated by improved body image parameters. The effect of weight loss on cardiometabolic risk factors related to sexual dysfunction requires dedicated longitudinal studies, with the use of objective methods. Disclosure No

Effectiveness of a Manual Therapy Protocol in Women with Pelvic Pain Due to Endometriosis: A Randomized Clinical Trial.

A randomized controlled trial was carried out to assess the effectiveness of a manual therapy protocol in terms of the clinical characteristics, quality of life, and emotional condition of the women with endometriosis-related pelvic pain. Forty-one women (mean age of 36.10 (6.97) years) with pelvic pain due to endometriosis were randomly divided into (i) a manual therapy group (MTG) (n = 21) and (ii) a placebo group (PG) (n = 20). Both groups received an 8-week intervention. Pain, lumbar mobility, endometriosis health profile, quality of life, depression and anxiety levels, and the patient's perception of change were assessed before (T0) and after (T1) the intervention, as well as at a one-month follow-up (T2) and a six-month follow-up (T3). The MTG significantly improved pain intensity, powerlessness, lumbar mobility, and physical quality of life at T1 (p < 0.05). The results were maintained for pain intensity at T2 and T3. In addition, both the MTG and PG improved emotional wellbeing at T1 (p < 0.05). Neither group improved in terms of social support, self-image, and depression and anxiety levels after the intervention (p > 0.05). In conclusion, manual therapy may be an excellent complement to the gynecological treatment of endometriosis-related pelvic pain by alleviating pain and improving women's endometriosis health profile and physical quality of life.

Enhanced Recovery After Surgery and Postoperative Nausea and Length of Stay in Mastectomy Patients With Reconstruction

IntroductionSurgery is a mainstay of curative breast cancer treatment and is associated with postoperative nausea and vomiting (PONV) negatively impacting the patient experience. Enhanced recovery after surgery (ERAS) protocols are a combination of evidence-based strategies applied to traditional perioperative practices with the goal to reduce postoperative complications. ERAS protocols have been traditionally underutilized in breast surgery. We investigated if the implementation of an ERAS protocol was associated with decreased rates of PONV as well as length of stay (LOS) in patients undergoing mastectomy with breast reconstruction. MethodsWe conducted a retrospective chart review case-control study in which we compared PONV and LOS between ERAS cases and non-ERAS controls. Our data set consisted of 138 ERAS cases and 96 non-ERAS controls. All patients were >18 y old and underwent mastectomy with immediate implant or tissue expander-based reconstruction between 2018 and 2020. The non-ERAS group consisted of procedure-matched controls that were treated prior to implementation of the ERAS protocol. ResultsIn univariate comparisons, patients who underwent the ERAS protocol had significantly decreased postoperative nausea (mean 37.5% of controls versus 18.1% of ERAS, P < 0.001) and shorter LOS (1.21 versus 1.49 d, P < 0.001). Using a multivariable regression to control for potential confounders, ERAS protocol was associated with less postoperative nausea (odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.13-0.5), LOS 1 d versus > 1 d (OR = 0.19, 95% CI = 0.1-0.35), and less postoperative ondansetron use (OR = 0.03, 95% CI = 0.01-0.07). ConclusionsOur results indicate that implementation of the ERAS protocol in women undergoing mastectomy with immediate reconstruction is associated with improved patient outcomes in postoperative nausea and LOS.

Enhanced recovery after gynecological surgery: A meta-analysis of randomized controlled trials.

Enhanced recovery after surgery protocol is a multidisciplinary and multimodal approach designed to improve perioperative outcomes for patients. This meta-analysis aimed to identify and elaborate on the efficacy of this protocol in women undergoing gynecologic surgery. Four databases were searched for randomized controlled trials from inception to December 2021. A total of 14 studies met the inclusion criteria and were analyzed. There was a significant reduction in the length of stay, the time to first flatus and first defecation, complications, and readmission rates in patients undergoing enhanced recovery after surgery when compared to routine care. The rate of discharge on the first postoperative day significantly increased in patients from the enhanced recovery group. There was no significant difference in the surgery time and blood loss. In conclusion, the enhanced recovery after surgery protocol might have a positive effect on patients undergoing gynecologic surgery. However, there is still heterogeneity between the included studies, and we need more research to draw reliable conclusions that enhanced recovery after surgery is favorable.

What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis.

Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety. A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment. A frequentist network meta-analysis combining direct and indirect comparisons (using the long GnRH agonist protocol as the comparator) was also performed to enhance the precision of the estimates. The systematic literature search was performed using Embase (Ovid), MEDLINE (Ovid), Cochrane Central Register of Trials (CENTRAL), SCOPUS and Web of Science (WOS), from inception until 23 November 2021. The search terms comprised three different MeSH terms that should be present in the identified studies: GnRH antagonist; assisted reproduction treatment; randomized controlled trial (RCT). Only studies published in English were included. The search strategy resulted in 6738 individual publications, of which 102 were included in the systematic review (corresponding to 75 unique studies) and 73 were included in the meta-analysis. Most studies were of low quality. One study compared a flexible protocol with a fixed Day 5 protocol and the remaining RCTs with a fixed Day 6 protocol. There was a lack of data regarding live birth when comparing the flexible and fixed GnRH antagonist protocols or cetrorelix and ganirelix. No significant difference in live birth rate was observed between the different pretreatment regimens versus no pretreatment or between the different pretreatment protocols. A flexible GnRH antagonist protocol resulted in a significantly lower OPR compared with a fixed Day 5/6 protocol (relative risk (RR) 0.76, 95% CI 0.62 to 0.94, I2 = 0%; 6 RCTs; n = 907 participants; low certainty evidence). There were insufficient data for a comparison of cetrorelix and ganirelix for OPR. OCP pretreatment was associated with a lower OPR compared with no pretreatment intervention (RR 0.79, 95% CI 0.69 to 0.92; I2 = 0%; 5 RCTs, n = 1318 participants; low certainty evidence). Furthermore, in the network meta-analysis, a fixed protocol with OCP resulted in a significantly lower OPR than a fixed protocol with no pretreatment (RR 0.84, 95% CI 0.71 to 0.99; moderate quality evidence). The surface under the cumulative ranking (SUCRA) scores suggested that the fixed protocol with no pretreatment is the antagonist protocol most likely (84%) to result in the highest OPR. There was insufficient evidence of a difference between fixed/flexible or OCP pretreatment/no pretreatment interventions regarding other outcomes, such as ovarian hyperstimulation syndrome and miscarriage rates. Available evidence, mostly of low quality and certainty, suggests that different antagonist protocols should not be considered as equivalent for clinical decision-making. More trials are required to assess the comparative effectiveness of ganirelix versus cetrorelix, the effect of different pretreatment interventions (e.g. progestins or oestradiol) or the effect of different criteria for initiation of the antagonist in the flexible protocol. Furthermore, more studies are required examining the optimal GnRH antagonist protocol in women with high or low response to ovarian stimulation.

Luteal Phase Stimulation in the Same Cycle Is an Effective Strategy to Rescue POSEIDON Poor Responders with No Embryos after the First Follicular Stimulation.

Poor responders may benefit from recruiting a 'second wave' of antral follicles within the same cycle. This concept forms the basis of double stimulation which has been named as 'DuoStim'. This protocol involves ovarian stimulation in both follicular and luteal phases with egg retrieval in each phase, respectively, to increase the number of oocytes and embryos in one menstrual cycle. This can be considered a potentially valuable option for women with poor ovarian reserve/response to maximise the number of oocytes retrieved in a single ovarian cycle in the shortest possible time. The aim of this study was to evaluate the efficacy of the DuoStim protocol in women classified as POSEIDON poor responders undergoing in vitro fertilization by comparing the embryological outcomes between the follicular and luteal phase stimulations in the same menstrual cycle. This was a retrospective cohort study of 131 patients who enrolled to undergo DuoStim cycles from January 2021 to Sept. 2022, at a IVF center in a tertiary care hospital. The follicular phase stimulation used a standard antagonist protocol for the first oocyte retrieval. Thereafter, the luteal phase stimulation was started 3 days after the first retrieval, with the same dose of gonadotropin along with a daily 10 mg medroxyprogesterone acetate tablet, followed by a second oocyte retrieval. Blastocysts produced in both the phases were subsequently vitrified. The paired t-test was used for comparing means and 95% confidence intervals (CIs) for different parameters. McNemar's test was used to compare paired proportions. The analysis was conducted using R statistical environment 4.2. The mean number of oocytes retrieved and the mean number of utilizable blastocysts frozen per stimulation cycle were found to be significantly higher in the luteal phase as compared to the follicular phase (5.71 ± 3.95 vs. 4.87 ± 2.79, P = 0.02, and 1.43 ± 1.22 vs. 0.95 ± 1, P = 0.001, respectively). However, the mean fertilization rate and the mean blastocyst utilization rate were found to be similar between both the phases. The length of stimulation was found to be approximately 3 days longer in the luteal phase (12.63 ± 2.43 vs. 9.75 ± 1.85, P = 0.001). Overall, the odds of obtaining a usable blastocyst in the luteal phase was found to be significantly higher than in the paired follicular phase (73.9% vs. 57.7%, P = 0.012, odds ratio: 2.286 [95% CI: 1.186-4.636]). Also importantly, the luteal phase stimulation was able to rescue 68% (32/47) of patients where no blastocysts were formed in the follicular phase. Our data demonstrate that in women with poor reserve, the addition of luteal stimulation could increase the chances of achieving a pregnancy by significantly increasing the number of eggs and transferable embryos per menstrual cycle compared to follicular stimulation alone. Furthermore, luteal phase stimulation in the same cycle proved to be an effective strategy to rescue POSEIDON poor responders with no embryos after the first stimulation.

Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian stimulation: a systematic review.

Endometriosis is an oestrogen-dependent disease that can cause subfertility in women who may require assisted reproductive technology (ART) to achieve their pregnancy goals. The aim of this study was to compare ART outcomes in women with endometriosis following the long GnRH-agonist controlled ovarian stimulation (COS) protocol with those taking the GnRH-antagonist COS protocol. MEDLINE, Embase and Web of Science were systematically searched in June 2022. Randomized controlled trials (RCTs) and observational studies comparing the long GnRH-agonist COS protocol and the GnRH-antagonist COS protocol in women with all stages/subtypes of endometriosis were included. Data were synthesized into comprehensive tables for systematic review. The Scottish Intercollegiate Guidelines Network (SIGN) checklists were used for the risk of bias assessment of non-randomized studies and randomized studies, and all the included studies were deemed to have acceptable quality. Eight studies (one RCT and seven observational) with 2695 patients (2761 cycles) were included. Most studies generally reported non-significant differences in clinical pregnancy or live birth rates regardless of the COS protocol used. However, the GnRH-agonist protocol may yield a higher total number of oocytes retrieved, especially mature oocytes. Conversely, the GnRH-antagonist protocol required a shorter COS duration and lower gonadotrophin dose. Adverse outcomes, such as rates of cycle cancellation and miscarriage, were similar between both COS protocols. Both the long GnRH-agonist and GnRH-antagonist COS protocols generally yield similar pregnancy outcomes. However, the long GnRH-agonist protocol may be associated with a higher cumulative pregnancy rate due to the higher number of retrieved oocytes available for cryopreservation. The underlying mechanisms of the two COS protocols on the female reproductive tract remain unclear. Clinicians should consider treatment costs, stage/subtype of endometriosis and pregnancy goals of their patients when selecting a GnRH analogue for COS. A well-powered RCT is needed to minimize the risk of bias and compare the risk for ovarian hyperstimulation syndrome. This review was prospectively registered at PROSPERO under Registration No. CRD42022327604.