Supplementation with vitamin D improves the embryo quality in in vitro fertilization (IVF) programs, independently of the patients' basal vitamin D status.

PURPOSE: The study aims to demonstrate the effects of Vitamin D (VD) supplementation, prior to oocyte pick-up within IVF protocols, in women with diverse VD status at the enrollment. METHODS: A total of 204 women eligible for intra-cytoplasmatic sperm injection (ICSI) cycles were included in the study and two homogeneous groups were selected from the database. Both group of patients with normal VD baseline level (> 40 ng/ml) and patients with low VD baseline level (< 20 ng/ml) were divided into control group and treatment group. The control group followed the standard procedure. The treatment group was supplemented with vitamin D3 as cholecalciferol in combination with Myo-Inositol, folic acid, and melatonin 3 months before standard procedure, once a day in the evening. RESULTS: VD levels significantly increased in the study group of low baseline VD, both in serum and in the follicular fluid compared to controls. The treatment induced a significant improvement of the embryo quality in both group of patients considered. CONCLUSION: Supplementation of VD in patients undergoing ICSI procedures significantly improved the number of top-quality embryos compared with the control group, either starting from VD normal baseline values or starting from low values. TRIAL REGISTRATION NUMBER: 07/2018.

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.

Impact of biomimetic electrical stimulation combined with Femoston on pregnancy rate and endometrium characteristics in infertility patients with thin endometrium: a prospective observational study.

OBJECTIVE: To explore the impact of biomimetic electrical stimulation combined with Femoston (estradiol tablets/estradiol and dydrogesterone tablets) on pregnancy rate and endometrium characteristics (endometrial thickness and type) in patients with infertility and a thin endometrium. METHODS: This prospective study enrolled patients with infertility and a thin endometrium admitted to Urumqi Maternal and Child Health Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China, between May 2021 and January 2022. The patients received Femoston alone (Femoston group) or Femoston combined with biomimetic electrical stimulation (electrotherapy group). The outcomes were the pregnancy rate and endometrium characteristics. RESULTS: Finally, 120 patients were enrolled (60/group). Before treatment, the endometrial thickness (p = 0.515) and the percentages of patients with endometrial types A + B and C (p = 0.769) were comparable between the two groups. After treatment, the endometrium of the patients in the electrotherapy group was thicker than those in the Femoston group (6.48 ± 0.96 mm vs. 5.27 ± 0.51 mm, p < 0.001). Furthermore, the percentages of patients with endometrial types A + B and C in the electrotherapy group were larger than in the Femoston group (p = 0.027). In addition, the pregnancy rates between the two groups (28.33% vs. 16.67%, p = 0.126) were similar. CONCLUSIONS: The results suggest the possibility that biomimetic electrical stimulation combined with Femoston could improve endometrial type and thickness in patients with infertility and thin endometrium compared with Femoston alone, but the pregnancy rate showed no significant improvement. The results need to be confirmed.

Assisted biomimetic electrostimulation therapy can improve the clinical pregnancy rate of patients with abnormal endometrial receptivity undergoing frozen-thawed embryo transfer cycles.

This study aimed to explore whether assisted biomimetic electrostimulation (BES) therapy can improve clinical outcomes in patients with abnormal endometrial receptivity undergoing frozen-thawed embryo transfer (FET) cycles. We retrospectively collected data from 132 patients who underwent FET cycles and divided them into the BES (n = 86) and non-BES (NBES) groups (n = 46). The clinical pregnancy rate (55.8 vs. 37.0%), biochemical pregnancy rate (59.3 vs. 41.3%), and live birth rate (44.2 vs. 23.9%) of the BES group were significantly higher than those of the NBES group (p < 0.05). No significant difference between the two groups was observed in endometrial thickness at FET day, embryo implantation rate, and early abortion rate (p > 0.05). The logistic regression analysis indicated that blastocyst transfer (adjusted OR = 3.617; 1.337-9.783; p = 0.011) and BES (adjusted OR = 2.398; 1.094-5.256; p = 0.029) were positively associated with the clinical pregnancy rate. These results suggested that assisted BES therapy can improve clinical outcomes in patients with diseases affecting endometrial receptivity.Impact statementWhat is already known on this subject? Biomimetic electrostimulation (BES) therapy can increase endometrial thickness in patients with thin endometria undergoing embryo transfers and to some extent improve their clinical outcomes.What do the results of this study add? Assisted BES therapy can improve clinical pregnancy rates in patients with abnormal endometrial receptivity undergoing FET cycles (55.8 vs. 37.0%, p = 0.039). After adjusting for covariates, BES was still positively associated with the clinical pregnancy rate (adjusted OR = 2.398; 1.094-5.256; p = 0.029).What are the implications of these findings for clinical practice and/or further research? BES therapy can improve endometrial receptivity. Further studies are needed to understand its specific mechanisms.

Effects of isoflavone supplementation on endometrial thickness, endometrial hyperplasia, and cancer in ovariectomized cats.

Ovariectomy is identified as a standard treatment in different European countries. Isoflavones, as nonsteroidal compounds in plants, are common constituents of soy and soy products. Some available cat diets contain different concentrations of soy products. This study aimed to examine the effects of isoflavone supplementation on endometrial hyperplasia and endometrial thickness in ovariectomized cats. Fifteen neutered adult cats were divided into control, estradiol, and isoflavone groups (five cats per group). Subcutaneous injection of estradiol (0.5 µg) in sesame oil (100 µL) was done for 30 days in estradiol-treated cats. Isoflavone-treated cats ingested a single oral tablet of soy extract for 30 days, while the controls received subcutaneous injections of the vehicle and oral placebo for 30 days. Histopathological findings of hematoxylin and eosin-stained sections revealed a significant difference between the estradiol group and other groups in terms of hyperplastic epithelium and simple hyperplasia. Thickness of myometrium was greater in the estradiol group compared to the isoflavone and control groups. Higher concentrations of estrogen can affect the endometrium and myometrium, while 30-day ingestion of isoflavone didn't have any uterine effect.

Correlation between bone mineral density and endometrial thickness over time in women with breast cancer history.

As the efficacy of chemotherapy and adjuvant endocrine therapy for breast cancer increase, the quality-of-life to cancer survivors could be more important issue in strategies of breast cancer treatment. Bone health has become more compelling in care of breast cancer survivor than ever before. This retrospective study was aimed to evaluate factors relating to the change in BMD and to ascertain the correlation between changes in BMD and EMT of women with breast cancer in follow-up. Records of 164 women who underwent surgery for breast cancer were reviewed in this study. The basal characteristics included parity, menopausal state, medication with vitamin D, bisphosphonate, selective estrogen modulator (SERM), aromatase inhibitor (AI), gonadotrophin releasing hormone agonist (GnRHa), chemotherapy, radiotherapy, cancer type including positivity of estrogen receptor, progesterone receptor and HER2, combined the other gynecologic disease or the other origin cancer. At initial and follow-up visit, all subjective were checked with BMD, endometrial thickness (EMT). The mean age was 52.1 ± 8.5 years old and overall interval between initial and follow-up visits were 17.6 ± 7.5 month in this study. The BMDs of L1-4 (1.040 ± 0.166 g/cm2 vs 1.070 ± 0.181 g/cm2, p < 0.001), femur neck (0.850 ± 0.121 g/cm2 vs 0.870 ± 0.136 g/cm2, p < 0.001), and femur total (0.902 ± 0.132 g/cm2 vs 0.915 ± 0.138 g/cm2, p < 0.001) at follow-up visit were significantly lower than those at initial visit. The change in BMDs of L1-4 (ΔBMDL1-4, r = 0.353, p < 0.001, and r = 0.228, p = 0.003), femur neck (ΔBMDNeck, r = 0.198, p = 0.011, and r = 0.282, p < 0.001), femur total (ΔBMDTotal, r = 0.294, p < 0.001, and r = 0.327, p < 0.001) had positive correlation with age and the change in EMT (ΔEMT). After age correction, ΔEMT had positive correlation with ΔBMDNeck (r = 0.245, p = 0.002) and ΔBMDTotal (r = 0.273, p < 0.001). ΔBMDL1-4 and ΔBMDNeck differed according to menopausal state (p < 0.001 and p = 0.035), bisphosphonate (p < 0.001 and p < 0.001), and GnRHa (p < 0.001 and p < 0.001). In follow-up of women with history of breast cancer, ΔEMT could be an alternative screening marker for BMD decrease.

Randomized controlled open-label study of the effect of vitamin E supplementation on fertility in clomiphene citrate-resistant polycystic ovary syndrome.

AIM: To evaluate the effect of vitamin E on ovulation and pregnancy in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). METHODS: A prospective, randomized, controlled, open label study was conducted on women with CC-resistant PCOS. Patients were randomized, to either control group (n = 30), who received metformin 500 mg thrice daily, in addition to 150 mg/day CC for 5 days starting from day 3 of menstruation for three menstruation cycles, or vitamin E group (n = 30) who received vitamin E 1500 IU/day for the whole study period in addition to metformin and CC with the same previous regimen. The primary outcome was cumulative ovulation rate, while secondary outcomes were pregnancy rate, serum midluteal progesterone, mean follicular diameter, number of dominant follicles and endometrial thickness. RESULTS: Ovulation was reported in 57 (64.8%) of 88 cycles in the control group and 63 (73.3%) of 86 cycles in the vitamin E group (P = 0.227), while pregnancy was reported in 4 (4.5%) of 88 cycles in the control group and 6 (7%) of 86 cycles in the vitamin E group (P = 0.491).There were nonsignificant differences between groups regarding serum midluteal progesterone, number of dominant follicles and mean follicular diameter. Endometrial thickness was significantly higher in the vitamin E group compared to the control group. CONCLUSION: The findings of this trial do not support the hypothesis that vitamin E may increase the ovulation and pregnancy rates in women with clomiphene citrate-resistant PCOS.

Effect of oral phytoestrogens on endometrial thickness and breast density of perimenopausal and postmenopausal women: A systematic review and meta-analysis.

BACKGROUND: Phytoestrogens constitute an alternative, non-pharmacologic approach for the management of menopausal symptoms. However, few studies have focused on their safety, specifically in relation to endometrial thickness and breast density. AIM: To systematically search for and quantitatively synthesize the evidence regarding the effect of phytoestrogens on endometrial thickness and breast density in perimenopausal and postmenopausal women. METHODS: Randomized controlled trials (RCTs) examining the effect of phytoestrogens compared with placebo or menopausal hormone therapy (MHT) on endometrial thickness and/or breast density in perimenopausal or postmenopausal women were searched for in the MEDLINE, CENTRAL and Scopus databases as well as "gray literature" sources until October 31, 2018. Main outcomes were the change from baseline in endometrial thickness and breast density. Statistical analysis was performed with RevMan 5.3, using R language and Open Meta-Analyst software. RESULTS: The meta-analysis for endometrial thickness included 30 RCTs (with a total of 3497 women), and that for breast density four RCTs (with a total of 674 women). Phytoestrogens did not affect endometrial thickness compared with placebo [weighted mean difference (WMD) -0.04 mm, 95% confidence interval (CI) -0.18 to 0.11, I2 66%] or MHT (WMD -1.40 mm, 95% CI -2.98 to 0.18, I2 84%). In addition, phytoestrogens did not affect breast density compared with placebo [standardized mean difference (SMD) -0.76, 95% CI -1.54 to 0.2, I2 95%). CONCLUSION: Phytoestrogens have no effect on endometrial thickness or breast density, when administered at various doses and for various durations, in perimenopausal and postmenopausal women. However, the high heterogeneity of the studies makes it necessary to conduct RCTs with less risk of systematic error.

[Effects of tongyuan acupuncture on pregnancy outcomes of ovarian induction period with clomiphene citrate: a retrospective analysis].

OBJECTIVE: To observe the clinical efficacy and action mechanism of tongyuan acupuncture for ovulatory disorder infertility of ovarian induction period with clomiphene citrate (CC). METHODS: Through retrospective analysis, 36 patients with ovulatory disorder infertility were divided into CC group (16 cases) and tongyuan acupuoture group (20 cases) by method. The patients in the CC group were treated with oral administration of CC (50 mg) for 5 days from the 5th day of menstruation; based on the treatment of CC, patients in the tongyuan acupuncture group were treated with tongyuan acupuncture; the group A of acupoint was mainly consisted of acupoints of the conception vessel and the three yin meridians and front-mu acupoints in abdomen; the group B of acupoint was mainly consisted of acupoints of the governor vessel and back-shu acupoints. The two groups of the acupoints were selected alternately, combined with the si-guan points (Taichong (LR 3)、Hegu (LI 4)) and five-shu points. The needles were inserted with flying needling method, and the needles were retained for 30 min per treatment; acupuncture was given once every other day. All the patients were treated for 2 months, and treatment stopped if pregnancy occurred. The pregnancy rate, cycle ovulation rate, maximum diameter of follicle, endometrial thickness and adverse effects were compared between the two groups. RESULTS: The pregnancy rate of the tongyuan acupuncture group was 75.0% (15/20), which was superior to 37.5% (6/16) in the CC group (P<0.05). The cycle ovulation rates of two groups were 70.4% (19/27, P>0.05). The maximum diameter of follicle and the endometrium thickness in the tongyuan acupuncture group were superior to those in the CC group (both P<0.05). The incidence of adverse effects in the tongyuan acupuncture group was 0% (0/20), which was lower than 18.8% (3/16) in the CC group (P<0.05). CONCLUSION: Tongyuan acupuncture combined with CC could improve the quality of follicle and the receptivity of endometrium in patients with ovulatory disorder infertility, so as to improve the pregnancy rate, which could be used as a safe and effective means to cooperate with modern assisted reproductive technology.

Efficacy and safety evaluation of Cimicifuga foetida extract in menopausal women.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of long-term treatment with Cimicifuga foetida extract in menopausal women. METHODS: A prospective, randomized, controlled clinical trial was conducted. A total of 96 early postmenopausal women were randomly assigned to three groups: group A received 1 mg estradiol valerate daily plus 4 mg medroxyprogesterone acetate on days 19-30; group B received 1 mg estradiol valerate daily plus 100 mg micronized progesterone on days 19-30; group C received 100 mg C. foetida extract daily. The efficacy was evaluated. Safety parameters were recorded. RESULTS: A total of 81 patients completed the treatment and follow-up visit. The modified Kupperman Menopausal Index scores decreased after 3 months in all groups. No significant changes were observed in the liver, renal function and components of metabolic syndrome in group C (p > 0.05). There were no significant differences in the incidences of metabolic syndrome among the three groups (p > 0.05). After 24 months, the endometrial thickness increased significantly in group B (p = 0.014), but not in the C. foetida extract group (p > 0.05). CONCLUSIONS: C. foetida extract is safe and effective for the treatment of menopausal symptoms in postmenopausal women.

Effects of acupuncture on pregnancy outcomes of ovarian induction period with clomiphene citrate: a retrospective analysis / 中国针灸

<p><b>OBJECTIVE</b>To observe the clinical efficacy and action mechanism of acupuncture for ovulatory disorder infertility of ovarian induction period with clomiphene citrate (CC).</p><p><b>METHODS</b>Through retrospective analysis, 36 patients with ovulatory disorder infertility were divided into CC group (16 cases) and acupuoture group (20 cases) by method. The patients in the CC group were treated with oral administration of CC (50 mg) for 5 days from the 5th day of menstruation; based on the treatment of CC, patients in the acupuncture group were treated with acupuncture; the group A of acupoint was mainly consisted of acupoints of the conception vessel and the three meridians and front- acupoints in abdomen; the group B of acupoint was mainly consisted of acupoints of the governor vessel and back- acupoints. The two groups of the acupoints were selected alternately, combined with the -guan points (Taichong (LR 3)、Hegu (LI 4)) and five- points. The needles were inserted with flying needling method, and the needles were retained for 30 min per treatment; acupuncture was given once every other day. All the patients were treated for 2 months, and treatment stopped if pregnancy occurred. The pregnancy rate, cycle ovulation rate, maximum diameter of follicle, endometrial thickness and adverse effects were compared between the two groups.</p><p><b>RESULTS</b>The pregnancy rate of the acupuncture group was 75.0% (15/20), which was superior to 37.5% (6/16) in the CC group (<0.05). The cycle ovulation rates of two groups were 70.4% (19/27, >0.05). The maximum diameter of follicle and the endometrium thickness in the acupuncture group were superior to those in the CC group (both <0.05). The incidence of adverse effects in the acupuncture group was 0% (0/20), which was lower than 18.8% (3/16) in the CC group (<0.05).</p><p><b>CONCLUSION</b> acupuncture combined with CC could improve the quality of follicle and the receptivity of endometrium in patients with ovulatory disorder infertility, so as to improve the pregnancy rate, which could be used as a safe and effective means to cooperate with modern assisted reproductive technology.</p>

Effect of Stage-based Acupuncture-moxibustion on Endometrial Thickness After Repeated Implantation Failure in IVF-ET / 上海针灸杂志

Objective To observe the effect of stage-based acupuncture-moxibustion therapy on the endometrial thickness in patients suffering from repeated implantation failure in IVF-ET (in vitro fertilization and embryo transfer). Method Seventy-two patients suffering from repeated implantation failure in IVF-ET were randomized into two groups. Thirty-six cases in the treatment group were intervened by stage-based acupuncture-moxibustion therapy plus oral administration of Estradiol valerate tablets; the other 36 cases in the control group were prescribed with oral administration of Estradiol valerate tablets alone. The implantation result of IVF-ET was analyzed 3 cycles later. The endometrial thickness was compared before and after the intervention. Result The endometrial thickness of the non-pregnant women increased after the treatment in both groups (P<0.05), and the increase in the treatment group was more significant than that in the control group (P<0.05). The clinical pregnancy rate in the treatment group was significantly higher than that in the control group (P<0.05). Conclusion Stage-based acupuncture-moxibustion therapy can improve the endometrial thickness, promote the growth of endometrium, benefit the implantation of embryo, and enhance the clinical pregnancy rate.

Adding Agnus Castus and Magnolia to Soy Isoflavones Relieves Sleep Disturbances Besides Postmenopausal Vasomotor Symptoms-Long Term Safety and Effectiveness.

The effectiveness for vasomotor symptoms and sleep disorders plus the long-term safety of a nutraceutical combination of agnus-castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli were assessed in postmenopausal women. A controlled study was carried out in menopausal women comparing this nutraceutical combination (ESP group) with a formulation containing isoflavones alone (C group) at the dosage recommended. The Kuppermann index, The Pittsburgh Sleep Quality Index (PSQI), and Short Form 36 (SF-36) were determined at baseline, three, six and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. One hundred and eighty women were enrolled in the study (100 in the ESP group and 80 in the C group). At the end of the treatment, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. The Kuppermann index and particularly the tendency for hot flashes progressively and significantly decreased in frequency and severity during ESP versus C treatment. At the same time, a significant increase in sleep quality and psychophysical wellness parameters was observed in the ESP versus C groups. No adverse events were observed. Agnus-castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. The endometrium, mammary glands and liver function were unaffected after 12 months of treatment.

Oral isoflavone supplementation on endometrial thickness: a meta-analysis of randomized placebo-controlled trials.

BACKGROUND: Isoflavone from soy and other plants modulate hormonal effects in women, and the hormone disorder might result in different caners including endometrial cancer. However, it's effect on the risk of endometrial cancer is still inconclusive. We aimed to assess the effects of isoflavone on endometrial thickness, a risk factor of endometrial cancer in peri- and post-menopausal women. METHODS: A meta-analysis of randomized controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endometrial thickness in peri- and post-menopausal women. Electronic searches were performed on the PubMed, Embase, the Cochrane Library, web of science, CINAHL, and WHO ICTRP to August 1st, 2015. Reviews and reference lists of relevant articles were also searched to identify more studies. Summary estimates of standard mean differences (SMD's) and 95%CIs were obtained with random-effects models. Heterogeneity was evaluated with meta-regression and stratified analyses. RESULTS: A total of 23 trials were included in the current analysis. The overall results did not show significant change of endometrial thickness after oral isoflavone supplementation (23 studies, 2167subjects; SMD:-0.05; 95%CI:-0.23, 0.13; P=0.60). Stratified analysis suggested that a daily dose of more than 54mg could decrease the endometrial thickness for 0.26mm (10 trials, 984subjects; SMD:-0.26; 95%CI:-0.45, -0.07; P=0.007). Furthermore, isoflavone supplementation significantly decrease the endometrial thickness for 0.23mm in North American studies (7 trials, 726 subjects; SMD:-0.23; 95%CI:-0.44, -0.01; P=0.04), but it suggested an increase for 0.23mm in Asian studies (3 trials, 224 subjects; SMD: 0.23; 95%CI:-0.04, 0.50; P=0.10). CONCLUSIONS: Oral isoflavone supplementation might have different effects in different populations and at different daily doses. Multiple-centre, larger, and long-term trials are deserved to further evaluate its effect.