Increase In Endometrial Thickness Research Articles

Strong Early Impact of Letrozole on Ovulation Induction Outperforms Clomiphene Citrate in Polycystic Ovary Syndrome.

Polycystic ovary syndrome is a common endocrine disorder, characterized by hyperandrogenism and/or chronic oligo/anovulation, which leads to infertility. The aim of this systematic review and meta-analysis was to explore the efficacy of letrozole compared with clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome. The study protocol has been registered with PROSPERO (registration number CRD42022376611). The literature search included randomized clinical trials. We conducted our systematic literature search across three medical databases: MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. The data synthesis employed a random effects model. Out of the 1994 articles screened, 25 studies fulfilled the inclusion criteria. The letrozole group exhibited a significant increase in endometrial thickness (mean difference = 1.70, confidence interval: 0.55-2.86; I2 = 97%, p-value = 0.008). The odds of ovulation (odds ratio = 1.8, confidence interval: 1.21-2.69; I2 = 51%, p-value = 0.010) and pregnancy (odds ratio = 1.96, confidence interval: 1.37-2.81; I2 = 32%, p-value = 0.002) were significantly higher. The resistance index of the subendometrial arteries showed a significant decrease (mean difference = -0.15, confidence interval: -0.27 to -0.04; I2 = 92%, p-value = 0.030). Women diagnosed with polycystic ovarian syndrome and treated with letrozole for ovulation induction had increased ovulation and pregnancy rates and increased endometrial thickness. The lower resistance index of subendometrial arteries can enhance intrauterine circulation, creating more favorable conditions for embryo implantation and development.

P-801 Sub-endometrial administration of angiogenic precursor cells and growth factors effectively optimizes endometrial thickness (EMT) and pregnancy outcomes in women with refractory thin endometrium

Abstract Study question Can hysteroscopic instillation of autologous blood derived progenitor cells combined with platelet derived growth factor concentrate into subendometrial region help patient with thin endometrium conceive? Summary answer Hysteroscopic subendometrial administration of stem cells represents a safe effective alternative method for patients recommended surrogacy, fail to improve despite using all possible treatment options What is known already Chronically thin endometrium is a challenge in ART, results in repeated expensive IVF cycles, cycle cancellations, unplanned cryopreservation of embryos and, surrogacy. Many studies have successfully used stem cells or platelet derivatives to rejuvenate reproductive tissues. When these growth-promoting cells and growth factors from platelets are delivered into basal layer which is origin of endometrial cells quality of the endometrium can be improved. While bone marrow is excellent source for obtaining stem cells main challenge is invasiveness of collection. This forms the basis for collecting mobilized endothelial progenitor cells from bone marrow into circulation for easy collection Study design, size, duration This study is to evaluate effect angiogenic precursor cells and growth factors derived from peripheral blood and bone marrow in improving endometrial quality and pregnancy outcomes. In the present pilot study involving 87 patients with persistent refractory thin endometrium were included and underwent frozen embryo transfer from April 2021-January 2024 at A4 fertility center, Chennai. All patients were treated with peripheral blood derived progenitor cells and platelet derived growth factors. Participants/materials, setting, methods 87 patients with EMT<7mm and >2 cancelled/failed cycles included. Two doses of SC-G-CSF were given on Menstrual Cycle Day 3&4, followed by venous blood aspiration on MCD-5. Seragen’s selective enrichment protocol was used to prepare circulating endothelial progenitor cells and growth factors concentrate. With 2.9mm hysteroscope and single lumen ovum pickup needle harvested cells and growth factors were injected on all four walls of cavity. Main results and the role of chance In this cohort, all patients presented refractory thin endometrium during hormone replacement therapy (HRT), despite exhaustive prior medication attempts. Subendometrial injection was employed, resulting in a significant increase in endometrial thickness (EMT) post peripheral blood cell injection (6.0 ± 0.71 vs. 7.80 ± 0.8; P = 0.0001), averaging a substantial improvement of 1.80mm. An optimal response, defined as EMT≥ 7mm, was observed in 47.2% (53) of cases. Patients with improved thickness underwent embryo transfer in the subsequent cycle, displaying a significant enhancement in endometrial thickness. Out of 53 patients, 47.2% (25) tested positive for β-HCG, while 45.3% (24) tested negative. Miscarriage occurred in 9.4% (5) of patients, with 8.8% (3) delivering healthy full-term babies. Notably, 28.3% (15) sustained uneventful pregnancies, accounting for a 34% sustained implantation rate. Comparatively, when benchmarked against subendometrial platelet-rich plasma (PRP) studies, primary and secondary outcomes in our study demonstrated superiority. This favorable outcome is attributed to the combined utilization of mobilized progenitor cells and growth factors. Prior research has established that the endometrium derives its stem cell content from the bone marrow, underscoring the efficacy of this novel approach. Limitations, reasons for caution Future research should explore avenues for women with refractory thin endometrium, offering conception options without resorting to surrogacy. Clinician expertise in patientselection, personalized dosage, and administration is crucial. While our study offers promising insights, its limitations include small sample size and lack of randomization, emphasizing need for larger, controlled trials. Wider implications of the findings Our study reveals that combine use of growth factors progenitor cells enhances endometrial thickness and improves pregnancy and live birth rates. Re-evaluating need for surrogacy in nonresponsive thin endometrium may be warranted. Insights from hematopoietic stem cell research offer reliable strategy for routine use in IVF clinical practice. Trial registration number Not applicable

Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study

Study objectiveTo evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion.DesignA prospective, randomized, controlled trial study.SettingA tertiary university hospital.PatientsA total of 130 patients with moderate (American Fertility Society [AFS] score of 5–8) and severe (AFS score of 9–12) intrauterine adhesions were recruited.Interventions86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD).Measurements and main resultsThe primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different.ConclusionInserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups.Trial registrationThis research was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/enIndex.aspx); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 (http://www.chictr.org.cn/showprojen.aspx?proj=17979). Date of trial registration: July 11, 2017.

Metformin ameliorates endometrial thickness in a rat model of thin endometrium.

Metformin, a well-established anti-diabetic drug, is also used in managing various other metabolic disorders including polycystic ovarian syndrome (PCOS). There are evidences to show that metformin improves endometrial functions in PCOS women. However, fewer studies have explored the direct effects of metformin on endometrium. Previous in vitro studies have shown that therapeutic serum concentrations of metformin enhance endometrial epithelial cell proliferation. The present study was undertaken to investigate in vivo effects of metformin on endometrial proliferation in a rat model of thin endometrium. Toward this, a rat model of thin endometrium was developed. Metformin (0.1% or 1% w/v) was administrated orally for 15 days in rats with thin endometrium. Oral metformin administration for three consecutive estrous cycles (15 days) in the thin endometrium rat model led to an increase in endometrial thickness compared to sham endometrium. Histological analysis showed a significant increase in the number of endometrial glands (P < 0.05), stromal cells (P < 0.01) and blood vessels (P < 0.01) in metformin-treated (n = 10 in each group) uterine horns compared to sham (saline-treated) uterine horns in rats. The expression of proliferating cell nuclear antigen and vascular epithelial growth factor was found to be upregulated on treatment with 1% metformin-treated group (n = 7). However, pregnancy outcomes in the rats treated with metformin remained unaltered despite the restoration of endometrial thickness. In conclusion, the study demonstrated that metformin ameliorates endometrial thickness in a rat model of thin endometrium by increasing endometrial proliferation and angiogenesis, without restoration of embryo implantation.

Эффективность комбинированной терапии комплексом противомикробных пептидов и цитокинов и природным антикоагулянтом прямого действия у пациенток с эндометриальным бесплодием: первые результаты сравнительного исследования

Aim: to evaluate the efficacy concerning the combined use of a complex including antimicrobial peptides and cytokines and a natural direct oral anticoagulant in female patients with endometriosis-associated infertility in the setting of thin endometrium Patients and Methods: the article presents a conducted comparative study. The main group (n=25) included therapeutic and restorative measures using a drug containing the complex of antimicrobial peptides and cytokines (vaginal suppositories 25U vaginally and rectally, alternating, for 40 days) in combination with natural direct oral anticoagulant (2 capsules per os, 3 times daily, for 20 days). Before the therapy initiation and 3 menstrual cycles after the treatment, biomarker levels in menstruation (proinflammatory cytokine IL-6), endometrial thickness (endometrial echo parameter) were measured in the main group, where its echostructure, hysteroscopy and optical spectroscopy data were also evaluated. The follow-up was lasting for 6 months after the treatment. The analysis and comparison of reproductive outcomes were conducted in the main group receiving the studied drugs and in the retrospective comparison group (n=56), which received traditional cyclic hormone therapy and a course of systemic magnet therapy Results: after the treatment course in the main group, there was a tendency to the IL-6 increase in menstrualtion, an increase in endometrial thickness (endometrial echo) to optimal values, as well as an increase in the parameters of endometrial oxygen consumption and its proliferative ability according to optical spectroscopy. In the main group who received the studied drugs, pregnancy occurred in 44±7.9% of cases, whereas in the comparison group — in 38±5.9% (p=0.2). Conclusion: the article has shown the combined use efficacy of drugs with antimicrobial peptides, cytokines and the natural direct oral anticoagulant in the treatment of endometriosis-associated infertility in the setting of thin endometrium. An increase in the IL-6 level in menstruation of the main group may indicate an inflammatory response activation from the endometrium ("cure through exacerbation"). It is necessary to continue research with a larger sample of patients and an assessment of additional parameters (microcirculation, tissue sensitivity) that characterize other links in the pathogenesis of endometriosis KEYWORDS: thin endometrium, endometriosis-associated infertility, menstruation biomarkers, diagnostic ultrasound, optical spectroscopy, complex of antimicrobial peptides and cytokines, natural direct oral anticoagulants. FOR CITATION: Motovilova T.M., Simakova V.Yu., Kachalina T.S., Borovkova L.V., Ponomareva I.V., Martiantseva I.V., Kruglova I.A., Lazukin V.F., Bogomolova M.D., Kazarinova D.A. The effectiveness of combination therapy with a complex of antimicrobial peptides and cytokines and a natural direct-acting anticoagulant in patients with endometrial infertility: first results of a comparative study. Russian Journal of Woman and Child Health. 2024;7(2):155–162 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-11.

Effect of combining estradiol valerate with sildenafil in increasing the thickness of the endometrium in infertile women before intrauterine insemination: a randomized clinical trial

Background: Therapies available for thin endometrium are limited and are mostly performed experimentally which most of these treatments have a similar function and increase blood flow to the endometrium, causing it to thicken and develop. The aim of the study was to compare the effect of estradiol valerate in combination with sildenafil on endometrial thickness in infertile women before intrauterine insemination. Methods: In this randomized clinical trial 100 infertile women referred to Reyhaneh Infertility Center in Ardabil were randomly divided into two groups. Patients' endometrial thickness was assessed by vaginal ultrasound before treatment and then on day 9 of the cycle. The intervention group received one tablet of estradiol valerate every 12 h from the ninth day of menstruation for 4 days and sildenafil as 25 mg orally daily from day 9 to 12, but in the control group, patients received placebo tablets orally in addition to estradiol. Results: There was no statistically significant difference between the intervention and control groups before and after the intervention in term of endometrial thickness. The rate of increase in endometrial thickness was 1.35 mm in the intervention group and 1.37 mm in the control group, but the difference was not statistically significant. Conclusions: Estradiol valerate alone or in combination with sildenafil resulted in a significant increase in endometrial thickness and increasing oral sildenafil supplementation with oral estradiol valerate had no significant effect on increasing endometrial thickness.

Autologous Platelet-Rich Plasma (PRP) Efficacy on Endometrial Thickness and Infertility: A Single-Centre Experience from Romania.

(1) Background: During IVF (in vitro fertilization), a proper endometrium thickness is one of the most difficult parameters to achieve and one of the most important prognostic factors of the success rate. One major problem is the high cancelation percentage in frozen embryo transfer cycles. The focus on the adjuvant methods for improving endometrium thickness is an on-going subject of interest. (2) Methods: This prospective single-arm self-control study was conducted in an IVF centre in Oradea, Romania. The patients were divided into two groups. The control group included 51 patients with at least one attempt to transfer a good-quality blastocyst, but the endometrial thickness did not surpass 7 mm under standard endometrial preparation protocol with oestradiol and with adjuvant therapy (other than PRP, such as aspirin, vitamin C, and vitamin E), and the study group included the same 51 patients that had the embryo transfer performed under the same standard endometrial preparation protocol with oestradiol preparation protocol and intrauterine PRP infusion. (3) Results: In our study, the PRP treatment had a positive impact on the parameters that were followed for the evaluation of the success rate of the embryo transfer procedure. The endometrial thickness (an increase in endometrial thickness by 0.6 mm after PRP treatment with p = 0.0001) and the clinical pregnancy rate (having a MD ± SD of 0 ± 0.38 before PRP treatment and with an increase to 0.5 ± 0.1 after the PRP treatment, p = 0.0004) were statistically significant (4) Conclusions: PRP has a positive effect in promoting endometrial proliferation, improving embryo implantation rate and clinical pregnancy rate for women with thin endometrium.

P-333 Thin endometrium, randomised clinical trial using plasma rich in growth factors

Abstract Study question Does the use of platelet growth factors instilled into thin endometrium in oestrogen-replacement treatment cycles improve endometrial thickness? Summary answer The use of growth factors in thin endometrium improves endometrial growth What is known already Thin endometrium impairs implantation rates and IVF outcomes. To date there is no effective treatment to improve the proliferation. PRGF-Endoret is used in multiple clinical indications. The autologous collection of growth factors (PRGF), applied to the area to be treated, produces a controlled release of multiple molecules with regenerative capacity in the focus of the lesion. Study design, size, duration Prospective randomised clinical trial to determine the effects of PRGF-ENDORET therapy in patients with thin endometrium undergoing oestrogen treatment for embryo transfer. Twenty-two patients were included from March 2018 to May 2021. At the end of the trial, a complementary retrospective study was conducted analysing all the treatments of these patients without live birth(21) before and after participating in the study until December 2022. 15 embryotransfer in study group and 27 in control group. Participants/materials, setting, methods Patients of IVI Bilbao clinic with endometrium less than or equal to 5mm after 10 days of treatment. PRGF was prepared according to the PRGF-Endoret technique using the medical device developed by BTI Biotechnology Institute. The study group received three instillations of PRGF Endoret using a kitazato IUI cannula. The first instillation was performed with in situ activated coagulum and the 2nd and 3rd instillations with PRGF-rich supernatants that were previously stored at -20 °C. Main results and the role of chance The clinical trial showed a significant increase in endometrial thickness 1.3 ± 0.67 mm compared to the control group of 0.58 ± 0.51 mm. Prior to treatment the mean endometrial thickness was 4.29 ± 0.88 in the control group and 4.44 ± 0.40 in the study group. After randomisation the mean was 4.87 ± 0.76 in the control group and 5.74 ± 0.87 in the study group. 2 pregnancies only in the study group and 1 live birth. The retrospective study shows 0.7mm increase in mean endometrial thickness in the post-PRGF cycles in the study group patients. Of the 15 transfers that were performed a posteriori, there were implantation rate of 40% and a 20% live birth rate, 40% biochemical miscarriage and 20% clinical miscarriage, with a significant increase of 0.94mm compared to the endometrium of the instillation cycle. In the control group of patients who received a posteriori factors there was also a significant increase in thickness of 1.6mm compared to the study cycle with an implantation rate of 58.33% and a 33% live birth rate, 58.33 biochemical miscarriage and 25% clinical miscarriage. Comparing all the cycles of these patients before and after PRGF, no statistical significance was found, although there was an increase of 0.29mm. Limitations, reasons for caution The number of patients included was lower than initially planned, but once the statistical power was adjusted, its safety and efficacy was demonstrated. More studies should be done to demonstrate when to instil, how many times, when transfer, but it is clear that it is safe and effective. Wider implications of the findings The use of factors has been shown to increase endometrial thickness. It could be thought to open the door to favouring endometrial receptivity and therefore live birth. Trial registration number 2016-001716-38

Features of ovarian steroidogenesis and endometrial hypertrophy during adjuvant therapy with tamoxifen in premenopausal patients with hormone-dependent breast cancer

Background. Difficulties in the prevention and treatment of endometrial pathology in hormone-positive breast cancer are associated with the lack of an unambiguous understanding of the mechanisms of the effect of tamoxifen on target tissues and the development of possible hyperestrogenism.Aim. To study the effect of ovarian steroidogenesis on the endometrium during adjuvant therapy with tamoxifen in pre-menopausal patients with hormone-dependent breast cancer.Materials and methods. All patients at inclusion in the study had intact menstrual function and received adjuvant therapy with tamoxifen. Group 1 included 42 patients without chemotherapy, group 2 included 41 patients with chemotherapy. Depending on the safety of the menstrual function, each group was divided into 2 subgroups. At the control points (3, 6 and 9 months from the start of tamoxifen therapy) patients underwent transvaginal ultrasound with measurement of endometrial thickness, and also determined the content of follicle-stimulating hormone and estradiol in peripheral blood. When menstruation persisted, blood sampling and measurement of endometrial thickness were performed on days 5-8 of the menstrual cycle.Results. In subgroups 1A and 2C, patients with preserved menstrual function showed a trend towards higher values of estradiol levels and endometrial thickness, compared with subgroups 1B and 2D of patients with amenorrhea. Against this background, the absence of statistically significant intergroup differences in the content of follicle-stimulating hormone in patients receiving tamoxifen with a preserved menstrual cycle (1A and 2C) and amenorrhea (1B and 2D) attracts attention. An intragroup analysis of follicle-stimulating hormone dynamics in patients with amenorrhea without chemotherapy in subgroup 1C shows an increase in its content by 162 %, without statistically significant changes in endometrial thickness and estradiol concentration. The statistically significant increase in endometrial thickness by 25 % and the proportion of patients with increasing endometrial wall thickness in 63.3 % in the 2D subgroup in patients receiving tamoxifen, with amenorrhea and previous chemotherapy treatment are cause for concern.Conclusion. The results of the study indicate a possible additive effect of such factors as intact menstrual function before the start of treatment for hormone-positive breast cancer, chemotherapy, and the development of amenorrhea on the progressive increase in endometrial thickness when using tamoxifen in premenopausal patients.

Hormone replacement therapy alone or in combination with tamoxifen in women with thin endometrium undergoing frozen-thawed embryo transfer: A retrospective study.

To investigate the effects of two protocols (hormone replacement therapy (HRT) alone or in combination with tamoxifen) on the endometrium and pregnancy outcome of patients with thin endometrium in frozen-thawed embryo transfer (FET) cycles. A total of 465 infertile patients with thin endometrium who underwent FET between January 2020 to June 2021 at the Drum Tower Hospital affiliated with Nanjing University Medical School were retrospectively analyzed. A total of 187 patients were given tamoxifen in addition to HRT (TMXF-HRT group), whereas 278 patients were given only HRT (HRT group). Clinical data were compared between the two groups, including general characteristics, endometrial thickness, and clinical pregnancy outcomes. There were no significant differences in baseline characteristics of all enrolled patients between two groups. Serum progesterone (P) was higher in HRT group than in the TMXF-HRT group (0.28 ± 0.53 ng/mL vs. 0.15 ± 0.25 ng/mL, P = 0.002). There was a significant increase in endometrial thickness in the TMXF-HRT group compared with the HRT group (OR: 1.54, 95% CI: 1.32-1.75, P < 0.001). There were no significant differences in the clinical pregnancy rate, embryo implantation rate, early miscarriage rate, or live birth rate between these two groups. Although tamoxifen when used in combination with hormone replacement therapy can significantly increase endometrial thickness, it may not have a role in improving the pregnancy outcomes of patients with thin endometrium undergoing FET cycles.

Hysteroscopic injections of autologous endometrial cells and platelet-rich plasma in patients with thin endometrium: a pilot randomized study

The aim of this study was to evaluate the efficacy of hysteroscopically controlled injections of autologous platelet-rich plasma (PRP) and autologous endometrial cells as a treatment for infertile women with thin endometrium. The study enrolled 115 patients with thin endometrium (< 7 mm at implantation window) and infertility, who were divided into groups: Group 1 (the control) underwent conservative therapy; Group 2 received intraendometrial PRP injections instead of the conservative therapy; Group 3 received identical injections after conservative therapy; Group 4 received injections of the autologous endometrial cells suspended in PRP. A single injection dose of PRP contained 0.6–0.7 × 1011 of platelets. The levels of PDGF-BB and VEGF in PRP were increased compared with ordinary plasma. The autologous endometrial cells, obtained from pipelle biopsies, constituted heterogeneous cell populations containing stromal and epithelial cells. Intraendometrial PRP injections had significant impact on endometrial thickness and local microcirculation in Group 2 and Group 3. In Group 4, injections of PRP reinforced with endometrial cells also facilitated a significant increase in endometrial thickness. This work describes a novel approach for infertility treatment in patients with refractory thin endometrium. PRP injections and injections of the endometrial cells suspended in PRP into endometrium enhanced cell proliferation and angiogenesis.

Asymptomatic endometrial thickening in postmenopausal women: predictor of malignant pathology?

It is not standardised what is the endometrial thickness that discriminates between normal and potentially malignant. The objective of this study was to determine the endometrial thickness cut-off point from which the risk of endometrial cancer (EC) increases in asymptomatic postmenopausal women; and to evaluate the risk factors linked to malignant endometrial pathology as well as other associated ultrasound findings. This was a retrospective observational study that included hysteroscopies performed at the Hospital Materno-Infantil on 267 asymptomatic menopausal women with an increase in endometrial thickness (AET) >5 mm, from 2015 to 2019. The results shows that the prevalence of malignant pathology in asymptomatic postmenopausal women with a casual finding of endometrial thickening was 3.7%. This percentage was 16.3% when the cut-off point of AET was established at 10 mm. There was a significant association for the diagnosis of malignant pathology with this cut-off point. There is a significant association between the 10 mm endometrial thickness cut-off point from which the risk of EC increases in asymptomatic postmenopausal women. Impact statement What is already known on this subject? Several studies have established the cut-off point for asymptomatic endometrial thickening (AET) for atypical endometrial hyperplasia and endometrial cancer at 10 mm. Although no cut-off point has optimal accuracy for the diagnosis of malignant endometrial pathology, it has been found that with a cut-off value of AET >10 mm no cases are missed. Likewise, a cut-off point of AET > 11 mm may provide a balance between cancer detection and histopathological workup extension. What do the results of this study add? A significant association was found at the cut-off point of AET > 10 mm, which suggests that screening postmenopausal women at this thickness is acceptable and unlikely to miss cases of endometrial hyperplasia and endometrial cancer. What are the implications of these findings for clinical practice and/or further research? After analysing our results we can conclude, like other published studies, that by establishing a cut-off point of 10 mm we obtain a good discrimination between benign and malignant pathology, which would allow us to diagnose 100% of malignant pathology. Above this cut-off point, the risk of endometrial cancer increases, and it would therefore be advisable to extend the study. A multicentre study is needed to confirm the cut-off point at which the risk of endometrial cancer increases in postmenopausal women with asymptomatic endometrial thickening.

The Effect of Human Growth Hormone on Endometrial Growth in Controlled Ovarian Hyperstimulation Cycles.

This study aims to compare endometrial growth before and after the addition of human growth hormone (hGH) in controlled ovarian hyperstimulation (COH) cycles. A 5-year retrospective cohort study of patients treated with hGH to improve oocyte development during COH cycles was conducted. Each patient's cycle without hGH immediately preceding cycle(s) with hGH was used for patients to serve as their own controls. Primary outcome was absolute growth in endometrial thickness from pre-stimulation start to day of hCG trigger. Mixed-model regression analysis controlled for patient correlation over repeat cycles and potential confounders. 80 patients were included. Mean age was 39.7 years; mean BMI was 23.8 kg/m2. Majority of patients were nulliparous, non-smoking, and White or Asian. Most common diagnosis was diminished ovarian reserve. Endometrial growth was compared between 159 COH cycles with hGH and 80 COH control cycles; mean increase was 4.5 mm and 3.9 mm, respectively-an unadjusted difference of 0.6 mm (95% CI: 0.2-1.1, p = 0.01). After adjusting for demographic/clinical factors, hGH was associated with 0.9 mm greater endometrial growth (0.4-1.4, p &lt; 0.01). Absolute increase in endometrial thickness was higher in COH cycles that included hGH. Further prospective studies in embryo transfer cycles are needed.

A clinical and immunological rationale for ultrasonic cavitation use in the complex treatment of infertility in chronic endometritis

Aim.To prove the safety and efficacy of using the ultrasonic cavitation of saline to restore the endometrial receptivity, local immune balance, and antioxidant status in females with chronic endometritis (CE) and a history of reproductive losses.&#x0D; Materials and methods. Fifty females aged 29.957.65 years (range 2338 years) with histologically and immunohistochemically confirmed CE were examined. The control group included 45 female patients aged 28.989.9 years (range 2338 years) with infertility of tubal-peritoneal genesis without histochemical studies confirming CE and with no history of reproductive losses. Transvaginal pelvic ultrasound was used in the study. All the patients had histological, immunohistochemical examination of endometrial scrapings, including quantification of CD138+, CD20+, CD56+, progesterone receptors (PR), and estrogen receptors (ER) in the stroma and glands. The following cytokines were measured in protein-free fractions of uterine cavity contents by ELISA: interleukin (IL)-2, IL-10, IL-8, tumor necrosis factor-, IL-1, interferon-, interferon-. The activity of lipoperoxidation factors and antioxidant system enzymes (catalase, superoxide dismutase, glutathione peroxidase) was detected by spectrophotometry. As a part of the treatment, irrigation of the uterine cavity with sonicated 0.9% sodium chloride solution was applied twice in 6 sessions consecutively within three months.&#x0D; Results. According to transvaginal pelvic ultrasound, the endometrial thickness before treatment was 6.541.2 mm. An increase in endometrial thickness up to 9.02 (7.6210.42) mm in the luteal phase of the next cycle and up to 9.34 (8.1210.56) mm in the two subsequent luteal phases was observed within three months after irrigation of the uterine cavity with sonicated normal saline. The normalization of the ЕR/PR ratio and decrease in CD138+, CD20+, and CD56+ cells in the endometrial stroma and glands were noted. Mature pinopods were revealed in 71.25 (67.2974.46)% of patients, which is 2.95 times more than the respect value before the treatment, 24.55 (21.4327.75)%. After treatment, a recovery of cytokine production was noted: IL-2, IL-10, tumor necrosis factor-, IL-8, IL-1, interferon-, interferon-; concentration of primary, secondary and tertiary products of lipoperoxidation decreased; superoxide dismutase enzyme activity increased by 36.98 (32.8841.18)%, catalase by 15.32 (14.1316.51)%, glutathione peroxidase by 12.32 (11.1214.2)%; р0,005. Reduced colonization rate of Streptococcus spp, Enterococcus faecalis, Escherichia coli, elimination of Mycoplasma genitalium, Ureaplasma urealyticum, and increased of Lactobacillus spp. were reported.&#x0D; Conclusion. Using the cavitated normal saline restores the endometrium structure, normalizes the ЕR/PR ratio, reduces the colonization by opportunistic and pathogenic microorganisms in the uterine cavity and normalizes the cytokine balance and the content of pro-oxidative and anti-oxidative factors. High clinical and immunological efficacy supports cavitated solutions in the complex treatment of infertility in females with CE.

The relationship of serum and follicular fluid pregnancy-associated plasma protein (PAPP-A) levels with endometrial thickness in PCOS and non-PCOS women undergoing ICSI-cycles

Pregnancy-associated plasma protein (PAPP-A) is a metalloproteinase that binds and cleaves insulin-like growth factor-binding protein 4 (IGFBP4), then releases IGF-1 from the IGFBP4/IGF-1 complex, activating the IGF pathway. As a result, in the IGF system, PAPP-A is regarded as a bioactive IGF-1 enhancing enzyme. IGFs and IGF receptors are thought to play a role in endometrium receptivity. A critical endometrium receptivity biomarker was up-regulated by PAPP-A. The present study aimed to assess the relationship of PAPP-A levels in serum and follicular fluid with endometrial thickness in PCOS and non PCOS women enrolled in the ICSI cycle. Forty-five infertile Iraqi women with PCOS and non-PCOS criteria were nominated from those who were attending the Higher Institute for Infertility Diagnosis and Assisted Reproductive Technologies clinic. The age of the included women ranged between 20-45 years. PAPP-A level measures in serum (at pick-up day and embryo transfer day) and follicular fluid. In non-PCOS patients, PAPP-A has higher level in serum and follicular fluid but without statistically significant difference comparing with PCOS patients. Level of PAPP-A and endometrial thickness increased significantly at the day of embryo transfer in contract with pick up day. The result did not show any correlation between PAPPA levels and endometrial thickness in both days. While, there was insignificant increase in endometrial thickness at both pick up and transfer days between pregnant and non-pregnant women. In conclusion, level of PAPP-A (in serum and follicular fluid) and endometrial thickness at the time of embryo transfer were significantly higher than pick-up day, this study did not establish a statistical significant relationship between serum and follicular fluid in PAPP-A levels and endometrial thickness.

Effects of autologous Platelet-Rich Plasma treatment on thin endometrium in patients undergoing frozen-thawed embryo transfer cycles

ObjectiveThe objective of this study is to determine whether the treatment of a thin endometrium with autologous platelet-rich plasma (PRP) prior to an embryo transfer increases positive reproductive outcomes in cycles where implantation failure is attributable to a thin endometrium, during the endometrial preparation cycles.Material and MethodsThis is a cohort, prospective and interventional study, carried out in a private facility. Women between 32 and 45 years old were included, with a history of two or more failed IVF/ICSI (In vitro fertilization/Intracytoplasmic sperm injection) cycles and a thin endometrium (&lt;7 mm), the cycles were with their own ovules or from donors not older than 28 years, with or without alterations in the seminal samples of their partners.Twenty-five women were enrolled in this study, the patients were treated with an intrauterine infusion of autologous PRP 2 or 3 times during the menstrual cycle on days 8, 10 and 12 of endometrial preparation for their frozen-thawed embryo transfer (FET) cycle, and Embryo Transfer (ET) was performed 3 to 5 days after the final autologous PRP infusion. A total of 25 patients underwent FET.ResultsOf 25 patients included in this study, the mean endometrial thickness after PRP treatment was 8.6 mm. The average increase in endometrial thickness was 1.76 mm this difference was statistically significant when compared with the previous cycles for each patient, respectively. The results of the cycles with PRP infusion treatment were compared with the previous results obtained in the same group of patients. The implantation, clinical pregnancy, and live birth rates (LBR) in the PRP treatment cycle were 24.59, 56, and 48%, respectively. Implantation, clinical pregnancy, and LBR in the control cycle were 0%. Implantation, clinical pregnancy, and LBR were significantly higher in the PRP treatment cycle than in the control cycle. Age, BMI, number of embryos transferred, and number of good quality embryos transferred were not significantly different.&#x0D; ConclusionsThe present study revealed a noticeable improvement in endometrial thickness after the PRP treatment considering the history of the patients, however, more studies are needed to elucidate the molecular basis of the PRP action mechanism on the endometrium and to support the results obtained and generate more solid evidence on the beneficial effect of autologous PRP treatment on the thin endometrium.

Histomorphometric analysis of the endometrium in an ectopic model of endometriosis in mice

Objective: Evaluate histomorphometry of ectopic and eutopic endometrial tissues in receptor mice. Method: Eighteen female Balb/c were divided into 3 groups, 6 animals each: GI Control, no procedure; GII – Sham, animals that had the same procedures as GIII without receiving the ectopic endometrial implant. Instead, they received saline solution; GIII – endometriosis model, animals had surgical intervention with an ectopic endometrial implant. GI and GIII mice were treated with 17β-estradiol, 100 µg/kg each. All animals were euthanized to collect uterine horns, which were fixed in 4% paraformaldehyde, embedded in paraffin, stained with Hematoxilin and Eosin and submitted to histomorphometric analyzes. Data underwent one-way ANOVA followed by Tukey’s test. Results: Local tissue growth, showing important lesions and adhesions, as well as dark cysts were noticed. In GIII group, there was an increase in number of blood vessels and glands (GIII ≥ GI and GIII p > .001). Thickening of the GIII endometrial epithelial was also evident (GIII ≥ GI and GIII. p > .001). We also noticed an increase in the number of eosinophils (GIII (GIII ≥ GI and GIII. p > .001). Conclusion: Easy to perform model, capable of reproducing morphological endometriosis characteristics. From our findings, there was an increase of endometrial thickness as well as an increase in the eosinophils population.

The Correlation Between Serum Pregnancy Associated Plasma Protein A (PAPP-A) with the Endometrial Thickness and Resistance Index and their Effect on Pregnancy Outcome for Infertile Women Undergo ICSI Cycle

Pregnancy-associated plasma protein-A (PAPP-A) is approved to be not pregnancy specific; it could be localized in nonpregnant women endometrium. Thus, it was of interest to see if PAPP-A can be capable of preparing the uterine endometrium for implantation. However, the relationship between serum PAPP-A and endometrium receptivity remains unclear. To evaluate if there is any correlation between the level of serum pregnancy associated plasma protein-A (PAPP-A) with the endometrial thickness and resistance index and evaluate their effects of pregnancy outcome for patient's candidate for intracytoplasmic sperm injection (ICSI). This is a prospective study that was submitted at the infertility center of High Institute for Infertility Diagnosis and Assisted Reproductive Technologies, Al-Nahrain University, Baghdad, Iraq, from November 2020 till March 2021. Forty-five infertile females participated in the study, younger than 40 years old submitted to antagonist protocol. For assessment of endometrium receptivity, transvaginal ultrasound was done at days of oocyte pickup and embryo transfer to measure the endometrial thickness and the resistance index. Serum PAPP-A was measured at the day of oocyte pickup and at day of embryo transfer. Two weeks later, a pregnancy test was done for all patients and according to the result the patients divided into two groups pregnant (n=20) and non-pregnant (n=25). There was insignificant positive correlation between serum PAPP-A level with endometrial thickness (ET) and insignificant negative correlation with (RI) at day of oocyte pick up and day embryo transfer. High serum Pregnancy associated plasma protein-A (PAPP-A) may be associated with an increase in endometrial thickness and low level of resistance index that both may promote the possibility of implantation.

Does endometrial thickness affect pregnancy outcomes in isolated male infertility IVF cycles? A retrospective cohort study

In our retrospective cohort study, we aimed to determine the role of endometrial thickness (ET) in isolated male factor infertile women in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo cycles. The patients were classified as having an endometrial thickness of <7 mm (n: 80), 7–9.9 mm (n: 335), 10–14 mm (n: 579) and >14 mm (n: 50) according to their ETs on the human chorionic gonadotropin (hCG) day. The overall clinical pregnancy rate was 37.4%, and no significant difference was found between the groups (p = .262). There was no significant difference between live birth rates (p = .094), but the highest pregnancy (46%) and live birth (34%) rates were found in the group with >14 mm ET. The increase in ET in IVF cycles increases pregnancy rates, albeit partially. When it is desired to determine a cut-off value, it can be said that pregnancy rates increase significantly in thicknesses of 14 mm and above. Impact Statement What is already known on this subject? When the literature is examined, many studies conclude that clinical pregnancy rates increase with the increase in endometrial thickness (ET) in IVF cycles, but there are also studies that argue the opposite. There is no study in the literature investigating the effect of ET on clinical pregnancy rates in patients with isolated male factor infertility. What do the results of this study add? In support of the literature, an increase in ET was found to be associated with an increase in clinical pregnancy rates, regardless of male and female factors. Although pregnancy occurs in thin endometriums, abortion rates are undesirably high. What are the implications of these findings for clinical practice and/or further research? Although the risk of abortion is high in thin endometriums, live birth rates are satisfactory. As a result, thin endometrium does not require cycle cancellation.

Clinicopathological features of endometrial lesions in asymptomatic postmenopausal women with thickened endometrium.

To analyze the clinical and pathological features of asymptomatic postmenopausal women with an incidentally detected increase in endometrial thickness (ET) by transvaginal ultrasound examination and discuss the cutoff value of ET for the timely discovery of endometrial malignancy. This was a retrospective study of postmenopausal women with asymptomatic thickened endometrium (greater than or equal to 5 mm) screened by transvaginal ultrasound who were referred to the gynecology department at Xuanwu Hospital between January 2018 and March 2021. Data on participant demographics, clinical characteristics, and histopathology outcomes were collected. We stratified the participants into the benign group and malignant group according to pathology results and assessed differences between the two groups. A receiver operating characteristic curve was used to identify the cutoff value of ET for predicting endometrial malignancy in postmenopausal women with asymptomatic thickened endometrium. A total of 163 eligible cases were included in the analysis. The results showed that only ET was significantly different between the two groups. The median ET was significantly higher in the malignant group than in the benign group (1.20 vs 0.80, P = 0.023). The optimal cutoff value of ET was 10 mmwith the maximum AUC (0.881, 95% CI 0.810-0.952, P = 0.024), and the sensitivity and specificity for the diagnosis of endometrial malignancy were 100%and 80%, respectively. Among the 47 women with ET ≥ 10mm, the prevalence of endometrial malignancy was 6.3%, which was significantly higher than that among women with ET < 10mm ( P = 0.023). For postmenopausal women with asymptomatic endometrial thickening, the prevalence of endometrial malignancy is significantly higher when ET is ≥ 10 mm. If ET is ≥ 10mm, further histopathological testing should be recommended to exclude endometrial malignancy. Further large-sample and prospective studies are needed to determine the predictive value of ET.