Assisted reproductive technology outcomes in women with congenital uterine anomalies: a systematic review.

PURPOSE: The present systematic review aimed to assess the fecundity of women with congenital uterine anomalies (CUAs) undergoing assisted reproductive technology (ART). METHODS: The present systematic review of the literature was reported according to the PRISMA guidelines. We systematically searched PubMed, MEDLINE, Embase and Scopus, from database inception to 17th October 2023. Studies were deemed eligible only if they included women with CUAs clearly fitting into one of the categories of the ASRM Müllerian anomalies classification 2021. RESULTS: Data relevant to the reproductive outcomes of women with CUAs who underwent ART were extracted from 55 studies. Regarding Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, studies on gestational surrogacy reported a live birth rate (LBR) ranging from 37 to 54%. Uterus transplant, although still experimental, showed promising results. Most studies reported a negative impact of unicornuate uterus and partial or complete septate uterus on both the miscarriage rate (MR) and the live birth rate (LBR). The reproductive prognosis of women with unicornuate uterus was shown to be particularly poor in case of twin pregnancy. Uterus didelphys, bicornuate and arcuate uterus seem not to negatively impact the ART reproductive outcomes. Uterus didelphys was associated with an increased risk of preterm birth (PTB), cesarean section and low birth weight (LBW). CONCLUSION: Women with CUAs should be informed regarding the impact (if any) of their congenital anomaly on both the chances of success of ART and on pregnancy-related complications. Elective single embryo transfer (eSET) should always be the first choice in patients with an increased baseline obstetric risk.

Vaginal Hysterectomy: A Network Meta-Analysis Comparing Short-Term Outcomes of Surgical Techniques and Devices.

OBJECTIVE: To provide available evidence comparing surgical outcomes of different vaginal hysterectomy (VH) techniques and devices. DATA SOURCES: PubMed, Embase, and ClinicalTrials.gov databases were searched from inception to December 1, 2023, using relevant keywords. METHODS OF STUDY SELECTION: Studies comparing at least 2 surgical techniques and devices for VH were included. An arm-based random effect frequentist network meta-analysis was performed. All available surgical outcomes were evaluated. TABULATION, INTEGRATION, AND RESULTS: Ten randomized controlled trials and 7 observational studies were eligible reporting on 1577 women undergoing VH with different techniques and devices (50% conventional, 22.5% Ligasure, 17.3% BiClamp, and 9.2% transvaginal natural orifice transluminal endoscopic surgery [vNOTES]). All surgical techniques/devices had a comparable risk ratio (RR) in terms of intraoperative complications, but Clavien-Dindo grade III postoperative complications were significantly reduced in the vNOTES group (RR, 0.15; 95% confidence interval [CI], 0.03-0.82; I2 = 0%) compared with conventional VH. The pooled network analysis showed a lower standard mean deviation for blood loss when comparing energy-based vessel sealing technologies (Ligasure: standard mean deviation, -0.92; 95% CI, -1.47 to -0.37; BiClamp: standard mean deviation, -1.66; 95% CI, -2.77 to -0.55) with conventional VH. Total operative time, postoperative hemoglobin variation, and pain were significantly reduced only in the Ligasure group compared with conventional VH. Bilateral salpingectomy or bilateral salpingo-oophorectomy was most commonly performed in the vNOTES group (RR, 1.9; 95% CI, 1.17-3.10) compared with the conventional VH group. CONCLUSION: Modern surgical techniques/devices have the potential to improve anatomic exposure and to reduce morbidity of VH. This may drive resurgence of vaginal approach to hysterectomy.

Untangling the independent effect of endometriosis, adenomyosis, and ART-related factors on maternal, placental, fetal, and neonatal adverse outcomes: results from a systematic review and meta-analysis.

BACKGROUND: Women with endometriosis may constitute a group at a particularly increased risk of pregnancy-related complications. Furthermore, women selected for assisted reproductive technology (ART) are exposed to additional endocrinological and embryological factors that have been associated with adverse pregnancy outcomes. OBJECTIVE AND RATIONALE: This study aimed to investigate the independent effect of endometriosis, adenomyosis, and various ART-related factors on adverse maternal, placental, fetal, and neonatal outcomes. SEARCH METHODS: Published randomized controlled trials, cohort studies, and case-control studies were considered eligible. PubMed, MEDLINE, ClinicalTrials.gov, Embase, and Scopus were systematically searched up to 1 March 2024. This systematic review and meta-analysis was performed in line with the PRISMA and the MOOSE reporting guidelines. To thoroughly investigate the association between endometriosis/adenomyosis and adverse pregnancy outcomes, sub-analyses were conducted, whenever possible, according to: the method of conception (i.e. ART and non-ART conception), the endometriosis stage/phenotype, the coexistence of endometriosis and adenomyosis, any pre-pregnancy surgical treatment of endometriosis, and the form of adenomyosis. The odds ratio (OR) with 95% CI was used as effect measure. The quality of evidence was assessed using the GRADE approach. OUTCOMES: We showed a higher risk of placenta previa in women with endometriosis compared to controls (34 studies, OR 2.84; 95% CI: 2.47, 3.26; I2 = 83%, moderate quality). The association was observed regardless of the method of conception and was particularly strong in the most severe forms of endometriosis (i.e. rASRM stage III-IV endometriosis and deep endometriosis (DE)) (OR 6.61; 95% CI: 2.08, 20.98; I2 = 66% and OR 14.54; 95% CI: 3.67, 57.67; I2 = 54%, respectively). We also showed an association, regardless of the method of conception, between endometriosis and: (i) preterm birth (PTB) (43 studies, OR 1.43; 95% CI: 1.32, 1.56; I2 = 89%, low quality) and (ii) cesarean section (29 studies, OR 1.52; 95% CI: 1.41, 1.63; I2 = 93%, low quality). The most severe forms of endometriosis were strongly associated with PTB. Two outcomes were associated with adenomyosis both in the main analysis and in the sub-analysis that included only ART pregnancies: (i) miscarriage (14 studies, OR 1.83; 95% CI: 1.53, 2.18; I2 = 72%, low quality) and (ii) pre-eclampsia (7 studies, OR 1.70; 95% CI: 1.16, 2.48; I2 = 77%, low quality). Regarding ART-related factors, the following associations were observed in the main analysis and confirmed in all sub-analyses conducted by pooling only risk estimates adjusted for covariates: (i) blastocyst stage embryo transfer (ET) and monozygotic twinning (28 studies, OR 2.05; 95% CI, 1.72, 2.45; I2 = 72%, low quality), (ii) frozen embryo transfer (FET) and (reduced risk of) small for gestational age (21 studies, OR 0.59; 95% CI, 0.57, 0.61; P < 0.00001; I2 = 17%, very low quality) and (increased risk of) large for gestational age (16 studies, OR 1.70; 95% CI, 1.60, 1.80; P < 0.00001; I2 = 55%, very low quality), (iii) artificial cycle (AC)-FET and pre-eclampsia (12 studies, OR 2.14; 95% CI: 1.91-2.39; I2 = 9%, low quality), PTB (21 studies, OR 1.24; 95% CI 1.15, 1.34; P < 0.0001; I2 = 50%, low quality), cesarean section (15 studies, OR 1.59; 95% CI 1.49, 1.70; P < 0.00001; I2 = 67%, very low quality) and post-partum hemorrhage (6 studies, OR 2.43; 95% CI 2.11, 2.81; P < 0.00001; I2 = 15%, very low quality). WIDER IMPLICATIONS: Severe endometriosis (i.e. rASRM stage III-IV endometriosis, DE) constitutes a considerable risk factor for placenta previa and PTB. Herein, we recommend against superimposing on this condition other exposure factors that have a strong association with the same obstetric adverse outcome or with different outcomes which, if coexisting, could determine the onset of an ominous obstetric syndrome. Specifically, we strongly discourage the use of AC regimens for FET in ovulatory women with rASRM stage III-IV endometriosis or DE. We also recommend single ET at the blastocyst stage in this high-risk population. REGISTRATION NUMBER: CRD42023401428.

Effect of type III female genital mutilation on obstetric outcomes: A systematic review and meta-analysis.

Background: Controversial evidence suggests a potential association between female genital mutilation (FGM/C) and adverse obstetric outcomes, with type III FGM/C (infibulation) carrying the greatest risk. The aim of this systematic review and meta-analysis was to assess current rate of adverse obstetric outcomes in women with type III female genital mutilation and cutting (FGM/C; infibulation) delivering across different settings worldwide. Methods: We searched PubMed, Scopus, Embase, and ClinicalTrials.gov databases from inception to Jan 1, 2023. Studies were selected if they included the main outcome of postpartum haemorrhage (PPH) or secondary outcomes, which included major conditions affecting maternal-neonatal health during labour and delivery. DerSimonian-Laird random effects meta-analysis including pooled effect estimates with corresponding 95 % confidence intervals was performed. Heterogeneity was assessed using the I2 statistic. Meta regression for relevant covariates was performed when data on relevant confounders were available. The Newcastle-Ottawa scale (NOS) was used to assess quality of observational studies. The level of evidence was assessed with the GRADE method. Results: 14 observational studies including 15,320 type III FGM/C women and 59,347 controls were eligible. The risk for postpartum haemorrhage was significantly increased in type III FGM/C, in the main analysis (OR 1.83, 95 % CI 1.03 to 3.24, I2 = 93 %), in pooling of data adjusted for confounders (aOR 1.76, CI 1.42 to 2.17, I2 = 0 %), and in sensitivity analysis of higher quality studies with NOS≥7 (OR 2.76, CI 1.38 to 5.51, I2 = 95 %). Meta-regression showed that nulliparity was significantly and positively associated with postpartum haemorrhage. Similarly, analysis of data adjusted for confounders showed an increased risk of episiotomy in type III FGM/C (aOR 1.56, CI 1.03 to 2.35, I2 = 52 %). Sensitivity analysis of studies with NOS≥7 revealed a significant increase for episiotomy (OR 7.53, CI 1.19 to 47.54, I2 = 96 %), perineal tears (OR 4.24, CI 1.09 to 16.46, I2 = 66 %), prolonged second stage of labour (OR 5.19, 95 % CI 1.00 to 26.85, I2 = 66 %), and Apgar score less than 7 (OR 4.19, CI 1.64 to 10.70, I2 = 0 %). No difference was found regarding obstetric anal sphincter injuries and mode of delivery in these women. Deinfibulation achieved similar obstetric and neonatal outcomes to women who never had type III FGM. The overall quality of the studies was adequate (median NOS score: 7; IQR: 6-8), the level of evidence, according to the GRADE assessment, was low. Conclusions: These results consistently show an increased risk of adverse obstetric outcomes in women with FGM/C type III. Infibulation substantially increases the risk for PPH, particularly in nulliparae. Systematic Review registration: PROSPERO CRD42023421993.

Opportunistic salpingectomy at the time of vaginal hysterectomy: A systematic review and meta-analysis.

BACKGROUND: Despite the rising rates of opportunistic salpingectomy at the time of surgery for non-malignant conditions, salpingectomy is not widely adopted during vaginal hysterectomy (VH) and has not been extensively investigated. OBJECTIVES: The aim of the primary study was to determine the feasibility of bilateral opportunistic salpingectomy at the time of VH. Secondary aims included surgical outcomes, factors associated with patient selection, and the prevalence of incidental tubal malignancies. SEARCH STRATEGY: In this systematic review and meta-analysis we searched Pubmed, Embase and ClinicalTrials.gov databases from inception to September 1, 2023, using relevant keywords. SELECTION CRITERIA: Original articles with no language restriction reporting outcomes of women undergoing planned VH with opportunistic salpingectomy, were considered eligible. Studies including patients undergoing VH with and without opportunistic salpingectomy were also included. DATA COLLECTION AND ANALYSIS: The Newcastle-Ottawa scale was used to assess quality of observational studies. DerSimonian-Laird random effects meta-analysis was performed and pooled effect estimates and proportions with corresponding 95% confidence intervals were computed. Heterogeneity was assessed using the I2 statistic. RESULTS: Seven observational cohort studies including 4808 women undergoing opportunistic salpingectomy at the time of VH and 10 295 patients undergoing VH alone were selected. The pooled proportion of success was 81.83 per 100 observations (95% CI: 75.35-87.54). Opportunistic salpingectomy at the time of VH, when feasible, was associated with a significant reduction in intraoperative complications (OR 0.06, 95% CI: 0.01, -0.37, P = 0.03) and total operative time (95% CI: -17.80, -1.07, P = 0.03) compared to those where it failed. Successful salpingectomy was significantly hindered by nulliparity (OR 0.12, 95% CI: -17.69, -1.21, P < 0.001) and favored by pelvic organ prolapse (OR 3.20, 95% CI: 1.35, 7.55, P = 0.008). Immunohistochemical tubal abnormalities were found in 13/579 (2.1%) patients. The overall quality of the evidence, according to the GRADE assessment, was low. CONCLUSION: Opportunistic salpingectomy is safe, effective, and feasible at the time of VH. Nulliparity and pelvic organ prolapse are factors potentially influencing surgical outcomes.

Neovagina creation methods in Müllerian anomalies and risk of malignancy: insights from a systematic review.

PURPOSE: This systematic review aims to provide a data synthesis about the risk of neovaginal cancer in women with Müllerian anomalies and to investigate the association between the adopted reconstructive technique and the cancer histotype. METHODS: PubMed, MEDLINE, Embase, Scopus, ClinicalTrials.gov and Web of Science databases were searched from inception to March 1st, 2023. Studies were included if: (1) only women affected by Müllerian malformations were included, (2) the congenital defect and the vaginoplasty technique were clearly reported, (3) the type of malignancy was specified. RESULTS: Literature search yielded 18 cases of squamous cell carcinoma and two cases of vaginal intraepithelial neoplasia 3 (VAIN 3). Of these, 3 had been operated on according to the Wharton technique, 8 according to the McIndoe technique, 3 with a split-skin graft vaginoplasty, 2 according to the Davydov technique, 2 with a simple cleavage technique, 1 according to the Vecchietti technique and 1 with a bladder flap vaginoplasty. A total of 17 cases of adenocarcinoma and 1 case of high-grade polypoid dysplasia were also described. Of these, 15 had undergone intestinal vaginoplasty, 1 had been operated on according to the McIndoe technique and 1 had undergone non-surgical vaginoplasty. Finally, 1 case of verrucous carcinoma in a woman who had undergone a split-skin graft vaginoplasty, was reported. CONCLUSION: Although rare, neovaginal carcinoma is a definite risk after vaginal reconstruction, regardless of the adopted technique. Gynaecologic visits including the speculum examination, the HPV DNA and/or the Pap smear tests should be scheduled on an annual basis.

Surgical repair of post-cesarean vesicouterine fistula: A systematic review and a plea for prevention.

BACKGROUND: Vesicouterine fistula (VUF) is a iatrogenic injury in the vast majority of cases. The worldwide increase of cesarean delivery rates is expected to lead to increased complications. OBJECTIVES: To assess current evidence on VUF pathogenesis and surgical management. SEARCH STRATEGY: Pubmed and Embase databases were searched from January 2000 to January 2023 using relevant key words. SELECTION CRITERIA: Only original articles including either transabdominal or transvaginal surgical routes for post-cesarean VUF repair, in English language, were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened the references for eligibility, data extraction, and assessment of methodologic quality. All available surgical outcomes were recorded. MAIN RESULTS: Of the 1160 studies retrieved, 67 were selected for analysis. Most of these were case reports, case series, or observational cohort studies including a total of 284 patients. The majority (78.6%) of patients had more than one cesarean section, and approximately 10% of them experienced an overt bladder injury and/or uterine rupture at the time of cesarean delivery. The supratrigonal part of the bladder was most commonly involved (92.5%). The majority of patients (88.8%) underwent delayed VUF repair through laparotomy. Length of stay and blood loss were significantly less in patients treated via a minimally invasive approach (P < 0.001 and P = 0.02, respectively). Most patients had double-layer bladder repair and single-layer uterine repair. The overall success rate was 100% on first attempt for each independent combination of different surgical approaches and techniques. Live birth following VUF repair was reported in 23 patients. CONCLUSIONS: Paying close attention to surgical details is crucial to reduce the incidence of this complication and recurrence rates. Double-layer bladder closure and delayed timing of repair of VUF are recommended.

Before Is Better: Innovative Multidisciplinary Preconception Care in Different Clinical Contexts.

CONTEXT: Implementation of pre-conception care units is still very limited in Italy. Nowadays, the population's awareness of the reproductive risks that can be reduced or prevented is very low. Purpose and main findings: We presented a new personalized multidisciplinary model of preconception care aimed at identifying and possibly reducing adverse reproductive events. We analyzed three cohorts of population: couples from the general population, infertile or subfertile couples, and couples with a previous history of adverse reproductive events. The proposal involves a deep investigation regarding family history, the personal histories of both partners, and reproductive history. PRINCIPAL CONCLUSIONS: Preconception care is still neglected in Italy and under-evaluated by clinicians involved in natural or in vitro reproduction. Adequate preconception counseling will improve maternal and fetal obstetrical outcomes.

Vesicouterine Fistula After Cesarean Delivery at Full Cervical Dilation.

IMPORTANCE: Vesicouterine fistula (VUF) is an iatrogenic consequence of cesarean section in the vast majority of cases. The worldwide increase of cesarean delivery rates is likely to be accompanied by a rise of this complication, and surgery is the mainstay treatment. OBJECTIVE: The aim of the study is to assess current evidence on VUF pathogenesis and management. STUDY DESIGN: The study is a case report and literature review on PubMed and Embase spanning over the past 2 decades. RESULTS: An early VUF developed after a cesarean section at full cervical dilation and concurrent incidental bladder injury. A transabdominal extravesical repair was performed 3 months after cesarean delivery. Both the cystotomy and hysterotomy were repaired in a double-layer fashion with no interposition flap. A contemporary literature review including 25 patients showed that VUF was repaired transabdominally in 21 patients (84%), and an open approach was adopted in 18 patients (85.7%). In most patients, the uterine side was closed with a single-layer suture and an interposition flap was used to reinforce the repair. Concomitant hysterectomy was performed in 6 patients (24%). Overall, successful term pregnancies were reported in 2 patients after VUF repair. CONCLUSIONS: Vesicouterine fistula is a rare event and is commonly associated with cesarean sections, especially those with a concurrent bladder injury. Careful and meticulous surgical technique may prevent the occurrence of this condition. Delayed repair and double-layer closure of both bladder and uterus, with or without an interposition flap, are recommended.

Different management strategies for cesarean scar pregnancy: Short-term outcomes and reproductive prognosis.

PURPOSE: To investigate the impact on future reproductive potential of systemic methotrexate (MTX) administration, uterine artery embolization (UAE) and expectant management as treatments of caesarean scar pregnancy (CSP) and to assess their efficacy and safety. BASIC PROCEDURES: We retrospectively analysed patients with a diagnosis of CSP treated in a five years' period (2014-2018). Hospitalization, hCG normalization, menstrual cycle recovery, ultrasound restitutio ad integrum times, reproductive desire accomplishment after the resolution of the picture, and outcomes of subsequent pregnancies were considered. Only patients for whom complete diagnosis, treatment and follow-up data were available could be considered for study entry. MAIN FINDINGS: A total of 21 patients were included. Three of them were managed expectantly. In two cases spontaneous abortion occurred and one case underwent caesarean delivery at 35 weeks of gestation for complete placenta previa with hysterectomy for post partum haemorrhage. Seven patients were treated with systemic MTX. Median [IQR] times of hospitalization, hCG normalization, menstrual cycle recovery and ultrasound restitutio ad integrum were 21 days [10-26 days], 52 days [18-64 days], 8 weeks [6-10 weeks] and 8 weeks [6-11 weeks] respectively. At the end of follow up, 80% (95%CI [38-96%]) of patients with reproductive desire achieved at least one live birth. Eleven patients were treated with UAE combined with MTX. Median [IQR] times of hospitalization, hCG normalization, menstrual cycle recovery and ultrasound restitutio ad integrum were 14 days [12-20 days], 43 days [30-52 days], 8 weeks [4-12 weeks] and 8 weeks [8-10 weeks], respectively. Of those who expressed a reproductive desire after treatment, 80% (95%CI [49-94%]) achieved at least one live birth. In all included patients, the menstrual cycle was restored. PRINCIPAL CONCLUSIONS: Reproductive potential of women treated for CSP was preserved after both systemic MTX administration and systemic MTX combined with UAE. Both strategies proved to be safe.

Efficacy of ferric carboxymaltose for treatment of iron deficiency anemia diagnosed in the third trimester of pregnancy: A case-control study.

AIM: To assess the efficacy of intravenous ferric carboxymaltose (IV FCM) for the treatment of iron deficiency anemia (IDA) diagnosed de novo in the third trimester of pregnancy. METHODS: Case-control study conducted in pregnant women with IDA newly diagnosed in the third trimester of pregnancy. Women treated with a single IV FCM injection were included as cases and those who received daily 210 g of oral ferrous sulphate (FS) as controls. Controls were matched to cases in a 2:1 ratio by basal hemoglobin (Hb) concentration (±0.5 g/dl). RESULTS: A total of 35 cases and 70 controls were included in the study. The mean Hb concentration level significantly increased after iron treatment in both cases (from 9.3 ± 0.8 to 11.1 ± 0.8 g/dl, p < 0.0001) and controls (from 9.6 ± 0.9 to 10.9 ± 1 g/dl, p < 0.0001). The rate of women who exceeded the recommended threshold of 11 g/dl after treatment did not significantly differ between cases (63% (95%CI, 45%-79%)) and controls (56% (95%CI, 44%-68%)) (p = 0.48). Comparison of maternal and neonatal outcomes and adverse effects did not show any significant difference between groups. CONCLUSIONS: Our results suggest that IV FCM and oral FS can be considered equally effective in the treatment of IDA newly detected in the third trimester of pregnancy.

Impact of Thyroid Autoimmunity on Assisted Reproductive Technology Outcomes and Ovarian Reserve Markers: An Updated Systematic Review and Meta-Analysis.

Background: Thyroid autoimmunity (TAI) has a high prevalence among women of reproductive age. Investigating its possible impact on ovarian function and fertility is, thus, of utmost relevance. The aim of this systematic review and meta-analysis was to elucidate the effect of TAI on both assisted reproductive technology (ART) outcomes and ovarian reserve. Methods: This systematic review and meta-analysis was restricted to two groups of research articles investigating the association between TAI and: (1) autologous ART outcomes (i.e., fertilization rate [FR], implantation rate, clinical pregnancy rate [CPR], miscarriage rate, and live birth rate), (2) markers of ovarian reserve (i.e., anti-Müllerian hormone, basal follicle stimulating hormone, antral follicle count, and number of oocytes retrieved). Studies including women affected by overt hypo/hyperthyroidism were excluded. Relevant studies were identified by a systematic search in PubMed, MEDLINE, ClinicalTrials.gov, Embase, and Scopus, from database inception to May 1, 2022. Results: From a total of 432 identified publications, 22 studies were included in Group 1 and 26 studies in Group 2. The presence of TAI was associated with a higher risk of miscarriage (7606 participants, odds ratio [OR] 1.52, confidence interval [CI 1.14-2.01], p = 0.004, I2 = 53%), lower chance of embryo implantation (7118 participants, OR 0.72, [CI 0.59-0.88], p = 0.001, I2 = 36%), and live birth (11417 participants, OR 0.73, [CI 0.56-0.94], p = 0.02, I2 = 71%). These associations were no longer observed in a subgroup analysis of patients who exclusively underwent intracytoplasmic sperm injection (ICSI). The FR and CPR as well as the mean values of surrogate markers of oocyte quantity appeared not to be affected by TAI. Conclusions: This data synthesis suggest a higher risk of adverse ART outcomes in women with positive TAI. However, the reliability of these findings is hampered by the relatively low quality of the evidence and significant heterogeneity in many of the meta-analyses. The possible protective effect of ICSI is promising but should be confirmed in controlled prospective clinical trials. PROSPERO Registration ID: CRD42021236529.

Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between the different endometrial preparation protocols for frozen embryo transfer (FET) and obstetric and perinatal outcomes? SUMMARY ANSWER: Programmed FET protocols were associated with a significantly higher risk of hypertensive disorders of pregnancy (HDP), pre-eclampsia (PE), post-partum hemorrhage (PPH) and cesarean section (CS) when compared with natural FET protocols. WHAT IS KNOWN ALREADY: An important and growing source of concern regarding the use of FET on a wide spectrum of women, is represented by its association with obstetric and perinatal complications. However, reasons behind these increased risks are still unknown and understudied. STUDY DESIGN, SIZE, DURATION: Systematic review with meta-analysis. We systematically searched PubMed, MEDLINE, Embase and Scopus, from database inception to 1 November 2021. Published randomized controlled trials, cohort and case control studies were all eligible for inclusion. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The quality of evidence was also evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies were included only if investigators reported obstetric and/or perinatal outcomes for at least two of the following endometrial preparation protocols: programmed FET cycle (PC-FET) (i.e. treatment with hormone replacement therapy (HRT)); total natural FET cycle (tNC-FET); modified natural FET cycle (mNC-FET); stimulated FET cycle (SC-FET). MAIN RESULTS AND THE ROLE OF CHANCE: Pooled results showed a higher risk of HDP (12 studies, odds ratio (OR) 1.90; 95% CI 1.64-2.20; P < 0.00001; I2 = 50%) (very low quality), pregnancy-induced hypertension (5 studies, OR 1.46; 95% CI 1.03-2.07; P = 0.03; I2 = 0%) (very low quality), PE (8 studies, OR 2.11; 95% CI 1.87-2.39; P < 0.00001; I2 = 29%) (low quality), placenta previa (10 studies, OR 1.27; 95% CI 1.05-1.54; P = 0.01; I2 = 8%) (very low quality), PPH (6 studies, OR 2.53; 95% CI 2.19-2.93; P < 0.00001; I2 = 0%) (low quality), CS (12 studies, OR 1.62; 95% CI 1.53-1.71; P < 0.00001; I2 = 48%) (very low quality), preterm birth (15 studies, OR 1.19; 95% CI 1.09-1.29; P < 0.0001; I2 = 47%) (very low quality), very preterm birth (7 studies, OR 1.63; 95% CI 1.23-2.15; P = 0.0006; I2 = 21%) (very low quality), placenta accreta (2 studies, OR 6.29; 95% CI 2.75-14.40; P < 0.0001; I2 = 0%) (very low quality), preterm premature rupture of membranes (3 studies, OR 1.84; 95% CI 0.82-4.11; P = 0.14; I2 = 61%) (very low quality), post-term birth (OR 1.90; 95% CI 1.25-2.90; P = 0.003; I2 = 73%) (very low quality), macrosomia (10 studies, OR 1.18; 95% CI 1.05-1.32; P = 0.007; I2 = 45%) (very low quality) and large for gestational age (LGA) (14 studies, OR 1.08; 95% CI 1.01-1.16; P = 0.02; I2 = 50%) (very low quality), in PC-FET pregnancies when compared with NC (tNC + mNC)-FET pregnancies. However, after pooling of ORs adjusted for the possible confounding variables, the endometrial preparation by HRT maintained a significant association in all sub-analyses exclusively with HDP, PE, PPH (low quality) and CS (very low quality). LIMITATIONS, REASONS FOR CAUTION: The principal limitation concerns the heterogeneity across studies in: (i) timing and dosage of HRT; (ii) embryo stage at transfer; and (iii) inclusion of preimplantation genetic testing cycles. To address it, we undertook subgroup analyses by pooling only ORs adjusted for a specific possible confounding factor. WIDER IMPLICATIONS OF THE FINDINGS: Endometrial preparation protocols with HRT were associated with worse obstetric and perinatal outcomes. However, because of the methodological weaknesses, recommendations for clinical practice cannot be made. Well conducted prospective studies are thus warranted to establish a safe endometrial preparation strategy for FET cycles aimed at limiting superimposed risks in women with an 'a priori' high-risk profile for obstetric and perinatal complications. STUDY FUNDING/COMPETING INTEREST(S): None. REGISTRATION NUMBER: CRD42021249927.

Post-partum Coronavirus Disease 19 Like Pneumonia Before the COVID-19 Italian Pandemic Outbreak: A Case Report.

Here we present a case of severe post-partum pneumonia that we observed at the end of January 2020. Specimen of blood was cultured and revealed Klebsiella pneumoniae bacteremia. However, the course of infection was atypical and the recovery time particularly long. Subsequently emerged COVID-19 hallmarks suggested to re-evaluate the case. After a multidisciplinary consultation, we concluded that, considering the clinical and imaging characteristics, the most likely hypothesis was that the patient was affected by novel Coronavirus pneumonia. The present case supports the hypothesis that Coronavirus might have circulated in northern Italy for weeks before its official detection.

Fertility in female cancer survivors: a systematic review and meta-analysis.

Data on the effects of cancer treatments on fertility are conflicting. The aim of the present systematic review and meta-analysis was to determine the chances of childbirth in women survivors of different types of cancer. PubMed, MEDLINE, Embase and Scopus were searched from database inception to 17 July 2019 for published cohort, case-control and cross-sectional studies that investigated the reproductive chances in women survivors of different cancer types. Random-effects models were used to pool childbirth hazard ratios, relative risks, rate ratios and odds ratios, and 95% confidence intervals were estimated; 18 eligible studies were identified. Childbirth chances were significantly reduced in women with a history of bone cancer (HR 0.86, 95% CI 0.77 to 0.97; I2 = 0%; P = 0.02 (two studies); RaR 0.76, 95% CI 0.61 to 0.95; I2 = 69%; P = 0.01 (two studies); breast cancer (HR 0.74, 95% CI 0.61 to 0.90 (one study); RaR 0.51, 95% CI 0.47 to 0.57; I2 = 0%; P < 0.00001 (two studies); brain cancer (HR 0.61, 95% CI 0.51 to 0.72; I2 = 14%; P < 0.00001 (three studies); RR 0.62, 95% CI 0.42 to 0.91 (one study); RaR 0.44, 95% CI 0.33 to 0.60; I2 = 95%; P < 0.00001 (four studies); OR 0.49, 95% CI 0.40 to 0.60 (one study); and kidney cancer (RR 0.66, 95% CI 0.43 to 0.98 (one study); RaR 0.69, 95% CI 0.61 to 0.78 (one study). Reproductive chances in women survivors of non-Hodgkin's lymphoma, melanoma and thyroid cancer were unaffected. Women with a history of bone, breast, brain or kidney cancer have reduced chances of childbirth. Thyroid cancer, melanoma and non-Hodgkin's lymphoma survivors can be reassured.

Prevalence and risk factors for restless legs syndrome during pregnancy in a Northern Italian population.

The objective of the present study was to investigate the frequency and the risk factors for restless legs syndrome (RLS) during pregnancy in an Italian population rarely studied, in epidemiological studies on the syndrome. A total of 648 women (median age: 35 years; interquartile range: 32-38), who delivered on randomly selected days at the obstetric department of our hospital, were identified. One hundred and thirty-two women (20.4%, 95% confidence interval (CI): 17.3-23.5) met the criteria for a diagnosis of RLS. The odds ratio (OR) of RLS was, in comparison with women aged <35 years, 1.69 (95% CI 1.14-2.51) in women aged ≥35 years. Subjective insufficient sleep (OR: 2.35, 95% CI 1.27-4.35) and difficulty in initiating sleep (OR: 1.73, 95% CI 1.15-2.63) increased the risk of RLS. This study confirms the high frequency of RLS in pregnant women. The risk of the condition was increased in women aged ≥35 years and in the women reporting sleep-wake disturbances during pregnancy. Impact statement What is already known on this subject? Restless legs syndrome (RLS), a common neurological, sensorimotor disorder, is two/three times more frequent in pregnant women than in the general population. The prevalence of RLS during pregnancy ranges widely, showing differences among populations. What do the results of this study add? This study adds data about the frequency and the risk factors for RLS during pregnancy in a Northern Italian population, rarely considered in epidemiological studies on the syndrome. Older age and sleep-wake disturbances are the main factors associated with the condition. What are the implications of these findings for clinical practice and/or further research? Screening for RLS might be useful for pregnant women to manage the condition. Further research is needed to investigate and define the potential impact of RLS during pregnancy on foetal and maternal health.

Observational prospective study on Lactobacillus plantarum P 17630 in the prevention of vaginal infections, during and after systemic antibiotic therapy or in women with recurrent vaginal or genitourinary infections.

We performed a prospective cohort parallel observational study on the use of Lactobacillus plantarum P 17630 in the prevention of vaginal infections. Eligible were women with a diagnosis of bacterial vaginosis (<15 days) and documented history of recurrent vaginal infections; and/or cystitis (<15 days); and/or treatment with antibiotics for bacterial respiratory tract infections during the week before the study entry. Study subjects were prescribed Lactobacillus plantarum P 17630 > 100.000.000 UFC one vaginal capsule per day for 6 days, then a capsule per week for 16 weeks. Eligible subjects were enrolled in two parallel cohorts: 85 women using (group A) and 39 not using (group B) Lactobacillus plantarum P 17630. The risk of recurrent infection within 4 months from the study entry, was higher among untreated women: multivariate OR 2.6 (95%CI 0.7-9.4). The modification of presence/intensity or symptoms was significant in both the study groups (p < .001). Impact statement What is already known on this subject? The Lactobacillus plantarum P 17630 has been shown to be active in the treatment of bacterial vaginosis and vaginal candidiasis. No data are available on its efficacy in the prevention of recurrent vaginal or urological infection or as a prevention strategy during systemic treatment with antibiotics. What do the results of this study add? This observational study suggests that Lactobacillus plantarum given for 4 months may lower the risk of recurrent infection in women with recurrent vaginal or genitourinary infection or after antibiotic systemic treatment for bacterial respiratory tract infection. The finding, however, is not statistically significant, possibly due to the lower than expected rate of infection observed in our population and consequently the limited power of the study. What are the implications of these findings for clinical practice and/or further research? New studies are needed in order to evaluate in different populations the role of Lactobacillus plantarum in lowering the risk of recurrent infection in a high-risk populations.

Fetal Doppler changes 1 week after endoscopic equatorial laser for twin-to-twin transfusion syndrome: A longitudinal study.

OBJECTIVE: To investigate sequential Doppler changes in donors and recipients before and 1 week after endoscopic laser for twin-to-twin transfusion syndrome (TTTS) and to examine factors that may be associated with such changes. METHODS: In TTTS pregnancies undergoing laser treatment, we examined fetal Doppler changes before and 1 week postintervention. Intrauterine death rates and preoperative factors were analyzed in relation to Doppler changes. RESULTS: Among 129 (85.4%) donors surviving at 1 week after laser, there was normalization of umbilical artery flow in 26 (72.2%) of 36 cases with preoperative abnormal Dopplers. In the remaining 10 (27.8%) fetuses, abnormal findings persisted. The rate of later intrauterine death was significantly higher in the latter group (6 of 10, 60.0%) compared with fetuses in which Doppler findings normalized (4 of 26, 15.4%; P < .05), with no difference in the rate of severe donor growth restriction between the 2 groups (80.0% vs 65.4%, respectively; P = .688). CONCLUSIONS: In about 70% of TTTS donors with preoperative abnormal umbilical artery Doppler, there was normalization 1 week after endoscopic laser. The incidence of fetal growth restriction was not significantly different in donors with persistence of Doppler abnormalities compared with those with normalized findings.