The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent IVF cycle ...outcome. Twenty-two RCTs and nineteen observational studies were included. Pooling of results showed a beneficial effect of intrauterine PBMC infusion on both CPR (RR 2.18; 95% CI 1.58-3.00; p < 0.00001; OR 2.03; 95% CI 1.22-3.36; p = 0.006) and LBR (RR 2.41; 95% CI 1.40-4.16; p = 0.002; OR 3.73; 95% CI 1.13-12.29; p = 0.03), of subcutaneous G-CSF administration on CPR (RR 2.29; 95% CI 1.58-3.31; p < 0.0001) and of intrauterine PRP infusion on CPR (RR 2.45; 95% CI 1.55-3.86; p = 0.0001). Observational studies also demonstrated a positive effect of IVIG and intrauterine hCG infusion on both CPR and LBR and of atosiban on CPR. Studies investigating intrauterine G-CSF infusion, LMWH, intravenous intralipid, hysteroscopy, blastocyst-stage ET, ZIFT, PGT-A and AH failed to observe an impact on IVF outcome. The quality of the evidence that emerged from RCTs focused on intrauterine PBMC infusion and subcutaneous G-CSF administration was moderate. For all other therapies/interventions it varied from low to very low. In conclusion, intrauterine PBMC infusion and subcutaneous G-CSF administration are the most promising therapeutic options for RIF. However, further well conducted RCTs are necessary before their introduction into clinical practice.
Objective To evaluate serum antimüllerian hormone (AMH) level modification after surgical excision of ovarian endometriomas. Design Systematic review. MEDLINE search from January 1990 to April 2012 ...using the combination of medical terms endometriosis, endometrioma, endometriotic cyst, and AMH or antimüllerian hormone, MIF or müllerian inhibiting factor. Reference lists of selected studies were checked for additional potential contributions. Setting Not applicable. Patient(s) Women with ovarian endometriomas requiring surgery. Intervention(s) Serum AMH level assessment. Main Outcome Measure(s) Serum AMH level modifications. Result(s) Eleven articles satisfied our selection criteria. Data pooling were deemed inopportune owing to the heterogeneity of the study designs and of the reported parameters. Nine of 11 studies documented a statistically significant reduction of serum AMH level after surgery. The two studies failing to document this decrease were published by the same study group and partly overlapped. The magnitude of the decline was more evident in women operated on for bilateral endometriomas. Conclusion(s) Evidence deriving from the evaluation of serum AMH level modifications after surgical excision of endometriomas supports a surgery-related damage to ovarian reserve.
Thyroid autoimmunity (TAI) is the most frequent autoimmune condition and the first cause of thyroid dysfunction among women of reproductive age. Notably, it has been associated with adverse obstetric ...outcomes during all trimesters of pregnancy. Furthermore, since most studies show an increased prevalence of TAI among women attending infertility clinics, a detrimental impact of this condition on natural fertility and on the rate of success of assisted reproductive techniques has been suggested. However, to date, the results have been inconsistent.
The objective of this study was to define the relation between TAI per se and the outcome of in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles.
A systematic literature review and meta-analysis were conducted. A Medline search was performed to identify all the comparative studies published from January 1990 to November 2015 in the English language literature on IVF/ICSI outcome in women with and without TAI, using combinations of the medical subject heading terms 'thyroid autoimmunity', 'thyroid autoantibodies', 'IVF', 'ICSI', 'pregnancy', 'miscarriage' and 'delivery'. The primary outcome was live birth rate (LBR). Our secondary outcomes were number of oocytes retrieved (NOR), fertilisation rate (FR), implantation rate (IR), clinical pregnancy rate (CPR) and miscarriage rate (MR). We also extracted data on mean age and basal serum concentrations of thyroid stimulating hormone (TSH) and performed a meta-regression analysis to assess the effect of these two covariates on CPR and MR.
We selected 12 studies for the meta-analysis. Six of the included studies were prospective cohort studies, and six were retrospective cohort studies. Compared with women with negative TAI, women with positive TAI had a lower LBR (odds ratio (OR) 0.73; 95% confidence interval (CI) 0.54-0.99; P = 0.04; 9 studies; 4396 women; I2 = 41%), a higher MR (OR 1.44; 95% CI 1.06-1.95; P = 0.02; 12 studies; 4876 women; I
= 35%), a similar CPR (OR 0.90; 95% CI 0.77-1.06; P = 0.22; 12 studies; 4876 women; I
= 7%), a similar number of oocytes (standardized mean difference SMD 0.10; 95% CI -0.09 to 0.29; P = 0.28; 5 studies; 1506 women; I
= 47%), a similar FR (OR 1.11; 95% CI 0.97-1.27; P = 0.13; 3 studies; 1082 women; I
= 0%) and a similar IR (OR 0.98; 95% CI 0.73-1.32; P = 0.91; 2 studies; 918 women; I
= 0%). Both mean age (SMD 0.96; 95% CI 0.66-1.27; P < 0.00001; 9 studies; 3256 women; I
= 85%) and serum TSH (SMD 0.24; 95% CI 0.15-0.34; P < 0.00001; 6 studies; 2098 women; I
= 59%) were higher in women with TAI. However, neither of these two covariates were significantly associated with CPR or MR.
TAI does not impact on IVF/ICSI outcome in terms of NOR and likelihood of fertilisation, implantation and clinical pregnancy. On the contrary, the presence of thyroid autoantibodies may have a detrimental effect on the course of a pregnancy, determining an increased risk of miscarriage and a decreased chance of live birth. However, given the possible modifying effects of age and serum TSH, further evidence is warranted prior to drawing inferences on causality.
Abstract
BACKGROUND
Anti-Müllerian hormone (AMH) serum concentration and antral follicle count (AFC), as measured by transvaginal ultrasonography, accurately reflect the antral follicle pool. ...However, AMH and AFC association with fertility surrogates (i.e. age at menopause, probability of conceiving naturally and ART success rate) is questioned. Miscarriage is often considered an alternative measure of reproductive capacity. Nonetheless, the impact of diminished ovarian reserve (DOR) on miscarriage incidence remains an understudied and unresolved issue.
OBJECTIVE AND RATIONALE
The aim of this systematic review and meta-analysis was to elucidate associations between DOR and miscarriage risk, both in women who conceived naturally and in those who achieved pregnancy through ART.
SEARCH METHODS
Relevant studies were identified by a systematic search in PubMed, MEDLINE, Embase and Scopus, from database inception to 1 March 2021. Studies were included only if all the following conditions were met: DOR was defined using serum AMH concentration or AFC; miscarriage rate was reported separately for different groups of women categorized according to the AMH and/or AFC level; authors reported either the rate of intrauterine pregnancy loss before 22 weeks of gestation or enough data were available to calculate it.
OUTCOMES
From a total of 347 publications initially identified, 16 studies were included. Pooled results from 13 retrospective studies focusing on ART pregnancies showed a significantly higher rate of miscarriage in women with a low AMH, as compared to women with a medium or high serum AMH concentration (12 042 women, random effects model, odds ratio (OR) 1.35; 95% CI, 1.10–1.66; P = 0.004; I2=50%). The only prospective study on ART pregnancies failed to show any association (61 women, risk ratio (RR) 2.95; 95% CI, 0.66–3.18; P = 0.16). Data from two prospective studies, which included naturally conceived pregnancies, showed a significantly increased miscarriage risk for women with low serum AMH. However, these data could not undergo meta-analysis owing to differing study designs. Using three retrospective studies, we observed an association between low AFC and miscarriage incidence (three retrospective studies on ART pregnancies, random effects model, OR 1.81; 95% CI, 1.02–3.21; P = 0.04; I2=64%).
WIDER IMPLICATIONS
Our meta-analysis findings suggest that within the DOR patient subgroup, serum AMH and AFC biomarker levels may correlate with both the quantitative and qualitative aspects of ovarian reserve. However, owing to study limitations, the aetiology of this effect remains unclear and we are unable to define a causal relationship between DOR and increased miscarriage or to provide clinical recommendations based on this information. However, if confirmed by future well-designed studies, these findings would be profoundly informative for guiding women in family planning decisions.
To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF).
Systematic review and meta-analysis.
Not applicable.
Women who ...achieved MZT and non-MZT pregnancies through IVF.
Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English.
Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection ICSI), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation.
A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the MZT and MCT pregnancy rate after IVF: (23 studies, OR 2.16, 95% CI, 1.74–2.68, I2=78%; 4 studies, OR 1.29; 95% CI, 1.03–1.62, I2=62%; and 3 studies, OR 1.90, 95% CI, 1.21–2.98, I2=59%; 2 studies, OR 2.34; 95% CI, 1.69–3.23, I2=0, respectively). Conventional IVF compared with ICSI and assisted hatching were associated with a statistically significantly increased risk of MZT pregnancy (9 studies, OR 1.19, 95% CI, 1.04–1.35, I2=0; 16 studies, OR 1.17, 95% CI, 1.09–1.27, I2=29%, respectively). Embryo biopsy for PGT-A or PGT-M, embryo cryopreservation, and oocytes donation were not associated with MZT pregnancies after IVF.
Blastocyst transfer is associated with an increased risk of both MZT and MCT pregnancies after IVF. Further evidence is needed to clarify the impact of female age, insemination method and AH on the investigated outcomes.
Factores de riesgo relacionados con el origen de gemelos monocigóticos tras fecundación in vitro: revisión sistemática y meta-análisis
Estudiar los factores de riesgo relacionados con el origen de gemelos monocigóticos (GMZ) y monocoriónicos (GMC) tras fecundación in vitro (FIV).
Revisión sistemática y meta-análisis.
No aplica.
Mujeres que gestaron GMZ y no GMC tras FIV.
Búsqueda sistemática en Medline de artículos en inglés publicados entre enero de 1995 y octubre de 2018.
Posibles factores de riesgo relacionados con el embarazo de GMZ y GMC tras FIV, tales como el cultivo prolongado, el método de inseminación (FIV convencional y microinyección intracitoplasmática ICSI), la biopsia embrionaria para el diagnóstico genético preimplantacional para la selección de aneuploidías o para las enfermedades monogénicas/ de un solo gen (DGP-A, DGP-M), la eclosión asistida (EA), la donación de ovocitos, la edad materna y la criopreservación embrionaria.
Un total de 40 estudios fueron incluidos. Se observó un incremento estadísticamente significativo de embarazos de GMZ y GMC tras FIV cuando se comparó la transferencia en estadio de blastocisto vs. la transferencia en estadio de células, así como cuando la edad materna era <35 años (23 estudios, OR 2.16, 95% IC, 1.74–2.68, I2=78%; 4 estudios, OR 1.29; 95% IC, 1.03–1.62, I2=62%; y 3 estudios, OR 1.90, 95% IC, 1.21–2.98, I2=59%; 2 estudios, OR 2.34; 95% IC, 1.69–3.23, I2=0, respectivamente). La biopsia embrionaria para DGP-A o DPG-M, la criopreservación embrionaria y la donación de ovocitos no se asociaron con los embarazos de GMZ y GMC tras FIV.
La transferencia en estadio blastocisto está asociada con un incremento de riesgo de embarazos de GMZ y GMC tras FIV. Para esclarecer el impacto de la edad materna, el método de inseminación y la EC en los resultados investigados, son necesarios más evidencias.
Defining whether medical therapy is effective in women with deep rectovaginal endometriosis and in which circumstances it can be considered an alternative to surgery is important for patients and ...physicians. Numerous observational and some randomized controlled studies demonstrated that different hormonal drugs improved pain and other symptoms in approximately two-thirds of women with deep rectovaginal endometriosis. Because major differences in the effect size of various compounds were not observed, much importance should be given to safety, tolerability, and cost of medications when counseling patients. Progestins seem to offer the best therapeutic balance when long-term treatments are planned. Women should be informed that hormonal drugs control but do not cure endometriosis and that, to avoid surgery, they should be used for years. Medical therapy is not an alternative to surgery in women with hydronephrosis, severe subocclusive bowel symptoms, and in those wishing a natural conception. A progestin should systematically be chosen as a comparator in future randomized trials on novel medications for deep endometriosis. In the meantime, the use of existing drugs should be optimized, and medical and surgical treatments could be viewed as subsequent stages of a stepwise approach. In general, there is no absolute “best” choice, and women must be thoroughly informed of potential benefits, potential harms, and costs of different therapeutic options and allowed to choose what they deem is better for them.
Endometriosis is characterized by frequent recurrences of symptoms and lesions even after extirpative surgery. Because medical therapies control but do not cure the disease, long periods of ...pharmacologic management may be needed until pregnancy desire or, sometimes, physiologic menopause. Hormonal drugs suppress ovulation and menstruation and have similar beneficial effects against pain. However, only estrogen-progestins and progestins have safety/tolerability/cost profiles that allow long-term use. These compounds induce atrophy of eutopic and ectopic endometrium, have antiinflammatory and proapoptotic properties, and can be delivered via different modalities, including oral, transdermal, subcutaneous, intramuscular, vaginal, and intrauterine routes. At least two-thirds of symptomatic women are relieved from pain and achieve appreciable improvements in health-related quality of life. Progesterone resistance may cause nonresponse in the remaining one-third. When using estrogen-progestins continuously, individualized, tailored cycling should be explained to improve compliance. All combinations demonstrated a similar effect on dysmenorrhea, independently from progestin type. Estrogen-progestins with the lowest possible estrogen dose should be chosen to combine optimal lesion suppression and thrombotic risk limitation. Progestins should be suggested in women who do not respond or manifest intolerance to estrogen-progestins and in those with dyspareunia and/or deep lesions. Progestins do not increase significantly the thrombotic risk and generally may be used when estrogens are contraindicated. Estrogen-progestins and progestins reduce the incidence of postoperative endometrioma recurrence and show a protective effect against endometriosis-associated epithelial ovarian cancer risk.
Probiotics are live microorganisms that, when administered in adequate amounts, should confer a health benefit to the host. Media sources tend to present probiotics as an appealing health promotion ...method able to prevent or treat a wide variety of clinical conditions. In obstetrics and gynaecology, Lactobacilli species are mainly used to restore the physiologic vaginal microbiota in order to treat bacterial vaginosis and vulvovaginal candidiasis (VVC) and prevent preterm birth.
Several RCTs investigated the potential benefits of probiotics in gynaecological and obstetrics conditions. For all potential indications, recent specific meta-analyses have been published. Considering vulvovaginal candidiasis in non-pregnant women, probiotics slightly improved the short-term clinical and mycological cure, and reduced the 1-month relapse. However, no important impact of probiotic use was observed on long-term clinical or mycological cure. Similarly, the addition of probiotics to metronidazole for the treatment of bacterial vaginosis was not shown to provide any additional benefit. In obstetrics, using probiotics during pregnancy neither decreased nor increased the risk of preterm birth before 34 weeks or before 37 weeks. Similarly, no benefits emerged for gestational diabetes, preterm premature rupture of membrane, and small and large for gestational age infants.
Despite increasing marketing of probiotics for the treatment of vulvovaginal candidiasis and prevention of preterm birth robust evidence demonstrating a beneficial effect is scarce. Moreover, there was considerable heterogeneity among the different studies in terms of route of administration, strain/s of probiotic adopted, and length of probiotic use. Before recommending the systematic use of probiotics to treat bacterial vaginosis and VVC and prevent preterm birth, high-quality research is needed. Professional medical associations should issue recommendations defining if, when, and how probiotics should be used for gynaecological disorders.
Objective To report the development of parasitic myomas after the use of a morcellator. Design Retrospective study. Setting Tertiary care referral center for the treatment of benign gynecologic ...pathologies. Patient(s) Women undergoing surgery for uterine fibroids. Intervention(s) Chart review. Main Outcome Measure(s) Presence of parasitic leiomyomas. Result(s) We identified four cases of parasitic myomas over the 3-year study period. Two out of the four were symptomatic. The prevalence of this complication, considering all women with whom the electric morcellator was used (n = 423) was 0.9% (95% CI, 0.3–2.2%). Considering exclusively the women who underwent myomectomy (n = 321), it was 1.2% (95% CI, 0.4–2.9%). Conclusion(s) Laparoscopic myomectomy with the use of a morcellator is associated with an increased risk of developing of parasitic myomas. A thorough inspection and washing of the abdominopelvic cavity at the end of the surgery should be performed to prevent this rare complication.
Abstract
STUDY QUESTION
Is infertility-related distress a risk factor for impaired female sexual function in women undergoing assisted reproduction?
SUMMARY ANSWER
Infertility-related distress, and ...especially social, sexual, and relationship concerns, is associated with female sexual dysfunction.
WHAT IS KNOWN ALREADY
Women with infertility are more likely to present sexual dysfunction relative to those without infertility. Moreover, assisted reproduction is associated with increased risk for female sexual problems. To date, this higher proportion of sexual impairment in infertile women has been simplistically linked to the stress associated with the condition and investigated risk factors included mainly demographic and clinical variables. Quantitative studies aimed at identifying risk factors for sexual dysfunction that also included the evaluation of infertility-related distress are conversely lacking.
STUDY DESIGN, SIZE, DURATION
This observational study was conducted at the Infertility Unit of the Fondazione Ca’ Granda, Ospedale Maggiore Policlinico of Milan between 2017 and 2018.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We included 269 consecutive patients with infertility aged 24–45 (37.8 ± 4.0 years). Sexual function outcomes were sexual dysfunction (assessed with the Female Sexual Function Index), sexual distress (evaluated with the Female Sexual Distress Scale-Revised), dyspareunia, and number of intercourses in the month preceding ovarian stimulation. Infertility-related distress was measured with the Fertility Problem Inventory (FPI). The effects of potential confounders such as demographic variables (women’s and partners’ age and level of education) and infertility-related factors (type and cause of infertility, number of previous IVF cycles, and duration of infertility) were also examined.
MAIN RESULTS AND THE ROLE OF CHANCE
Women with higher infertility-related distress were more likely to report sexual dysfunction (odds ratio = 1.02 per point of score; 95% CI, 1.01–1.03; P = 0.001). Three FPI domains (i.e. social, relational, and sexual concerns) were correlated with almost all sexual function outcomes (Ps < 0.05).
LIMITATIONS, REASONS FOR CAUTION
Women who were not sexually active were not included, thus reasons for sexual inactivity should be further explored in future studies. Data regarding men (e.g. sexual function and infertility-related distress) were lacking, thus cross-partner effects were not examined. Recall bias (also due to the fact that questionnaires were administered on the day of oocytes retrieval) and social desirability bias may have also affected women’s responses to the questionnaires.
WIDER IMPLICATIONS OF THE FINDINGS
Social, relational, and sexual concerns should be assessed and addressed in psychological counselling with the infertile couple.
STUDY FUNDING/COMPETING INTEREST(S)
None.
TRIAL REGISTRATION NUMBER
Not applicable.
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