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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 × 10 11 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.

PurposeStandard oocyte in vitro maturation (IVM) usually results in lower pregnancy rates than in vitro fertilization (IVF). IVM preceded by a prematuration step improves the acquisition of oocyte developmental competence and can enhance embryo quality (EQ). This study evaluated the effectiveness of a biphasic culture system incorporating prematuration and IVM steps (CAPA-IVM) versus standard IVM in women with polycystic ovarian morphology (PCOM).MethodsEighty women (age < 38 years, ≥ 25 follicles of 2–9 mm in both ovaries, no major uterine abnormalities) were randomized to undergo CAPA-IVM (n = 40) or standard IVM (n = 40). CAPA-IVM uses two steps: a 24-h prematuration step with C-type natriuretic peptide-supplemented medium, then 30 h of culture in IVM media supplemented with follicle-stimulating hormone and amphiregulin. Standard IVM was performed using routine protocols.ResultsA significantly higher proportion of oocytes reached metaphase II at 30 h after CAPA-IVM versus standard IVM (63.6 vs 49.0; p < 0.001) and the number of good quality embryos per cumulus-oocyte complex tended to be higher (18.9 vs 12.7; p = 0.11). Clinical pregnancy rate per embryo transfer was 63.2% in the CAPA-IVM versus 38.5% in the standard IVM group (p = 0.04). Live birth rate per embryo transfer was not statistically different between the CAPA-IVM and standard IVM groups (50.0 vs 33.3% [p = 0.17]). No malformations were reported and birth weight was similar in the two treatment groups.ConclusionsUse of the CAPA-IVM system significantly improved maturation and clinical pregnancy rates versus standard IVM in patients with PCOM. Furthermore, live births after CAPA-IVM are reported for the first time.

Background Oxidative stress (OS), defined as an imbalance between excessive reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) production and antioxidant insufficiency, has been suggested to be involved in the pathogenesis of poor ovarian response (POR). Growth hormone (GH) can reduce OS in some cell types. This study investigated whether GH can improve OS and the in vitro fertilization and embryo transfer (IVF-ET) outcomes of poor ovarian responders. Methods This study enrolled 105 patients with POR and 58 patients without POR (controls) who were diagnosed according to the Bologna criteria and underwent conventional IVF-ET. Poor ovarian responders were randomly assigned to two groups: the POR-GH group, which received pretreatment with GH 4 IU/d on day 2 of the previous menstrual cycle before IVF until the trigger day, and the POR-C group, which received no pretreatment. OS markers in follicular fluid (FF), ROS levels in granulosa cells (GCs), and the IVF outcomes of the groups were compared. Results Endometrial thickness on trigger day, the number of cleaved embryos, the number of higher-quality embryos, and the rates of embryo formation, higher-quality embryo formation, implantation and clinical pregnancy were significantly increased in the POR-GH group compared with the POR-C group ( P  < 0.05). Moreover, compared to those in the non-POR group, FF malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI) and ROS levels in GCs were significantly higher, whereas superoxide dismutase (SOD) and the total antioxidant capacity (TAC) were significantly lower in the POR-C group ( P  < 0.05). Furthermore, compared with those in the POR-C group, the FF TAC was significantly increased in the POR-GH group, and TOS, OSI and intracellular ROS levels were significantly reduced ( P  < 0.05). Conclusions Pretreatment with GH alleviates OS and improves oocyte quality and IVF outcomes of poor ovarian responders. Trial registration Chinese Clinical Trial Registry. ChiCTR1900021269 . Registered 8 February 2019, http://www.chictr.org.cn/edit.aspx?pid=35837&htm=4 .

ObjectivesThis study aimed to evaluate the role of intracytoplasmic sperm injection (ICSI) in the treatment of non-male factor infertile patients aged ≥ 39.MethodsThis is a single-center, prospective, randomized controlled clinical trial, between March 2018 and December 2019. Sixty-nine patients were recruited, and sixty patients participated in the study. Their ovaries were randomized prior to the beginning of the ovarian stimulation: the oocytes from one side (n = 257) were allocated to the ICSI (ICSI arm), while those of the contralateral side (n = 258) were allocated to conventional insemination (IVF arm). The fertilization rate per oocyte retrieved, number of zygotes (2PN), and cleavage-stage embryos were assessed and compared between the two study groups.ResultsThe average number of zygotes (3.1 vs. 2.7 p = 0.45), the fertilization rate (72.4% vs. 65.1% p = 0.38), the average number of cleavage-stage (2.8 vs. 2.4 p = 0.29), and the average top-quality embryos (TQE) cleavage-stage embryos (1.7 vs. 1.6 p = 0.94) were comparable between the two groups. The TQE rate per randomized oocyte (41.2% vs. 41% p = 0.8) was also similar in both groups.ConclusionsICSI does not improve the reproductive outcomes of advanced-age patients undergoing conventional insemination for non-male factor infertility.Trial registrationNCT03370068

Background The use of progestin (P) during ovarian stimulation is effective in blocking the luteinizing hormone (LH) surge in women with normal ovarian reserve, however, its effects have not been determined in poor responders. This study aimed to explore the follicular dynamics in P-primed minimal stimulation in poor responders. Methods A total of 204 infertile women with diminished ovarian reserve were allocated into the medroxyprogesterone acetate (MPA) group or the natural-cycle control group in an alternating order. MPA (10 mg) was administered daily beginning from the early follicular phase and a low dose of hMG was added in the late follicular phase if the serum FSH level was lower than 8.0mIU/ml. When a dominant follicle reached maturity, triptorelin 100 μg and hCG 1000 IU were used for trigger, and oocytes were retrieved 34-36 h later.All viable embryos were cryopreserved for subsequent frozen embryo transfer. Natural cycle IVF was used as controls. Results Compared with the natural cycle group, the MPA group exhibited a larger pre-ovulatory follicle (18.7 ± 1.8 mm vs 17.2 ± 2.2 mm), a longer follicular phase (13.6 ± 3.6 days vs 12.3 ± 3.2 days), and higher peak oestradiol values (403.88 ± 167.16 vs 265.26 ± 122.16 pg/ml), while maintaining lower LH values ( P  < 0.05). The incidences of spontaneous LH surge and premature ovulation decreased significantly (1.0% vs 50%; 2% vs. 10.8%, respectively; P  < 0.05). A greater number of oocytes and viable embryos were harvested from the MPA group than from the natural cycle group ( P  < 0.05). Moreover,the clinical pregnancy rate was slightly higher in the MPA group than in the natural cycle controls, but the difference was not significant (11.8% vs 5.9%, P  > 0.05). Conclusion This study supported the hypothesis that P-primed minimal stimulation achieved ovulation control of the dominant follicle and did not adversely affect the quality of oocytes in poor responders. Therefore, P-priming is a promising approach to overcome premature ovulation in minimal stimulation for poor responders. Trial registration ChiCTR-OCH-14004176 . Registered on January 8, 2014.

Background The presence of submucous fibroids strongly impacts on IVF results, therefore, these patients should be considered for surgical or medical treatment. The aim of this study was to assess the role of Ulipristal acetate (UPA), a selective progesterone receptor modulator, in restoring uterine cavity deformation due to submucous fibroids, in infertile patients attempting an IVF treatment. The secondary study outcome was to evaluate the impact of preconception UPA treatment on rate of biochemical pregnancy, ongoing pregnancy, and live birth compared to a control group without fibroids. Methods Infertile patients with submucosal fibroid (Type 1 and Type 2 according to FIGO classification) were enrolled in the study as fibroids group and received 1 to 3 treatment cycles of UPA, according to their response, as reflected by fibroid volume reduction and restoration of normal uterine cavity. Patients in control group were randomly selected from a general IVF cohort by a ratio of 2:1 with fibroids group, matched by age, BMI, type and cause of infertility and antral follicle count. The impact of UPA on fibroids volume reduction was evaluated. IVF outcome was compared between groups. Results Twenty-six patients underwent UPA treatment revealed a mean volume reduction of their fibroids of 41%. A total of 15 (57.6%) biochemical pregnancy were obtained, resulting in 13 (50%) ongoing pregnancy and 9 (34.6%) healthy babies were already delivered. Similar results were obtained in control group. Conclusion Restoration of normal uterine cavity by UPA treatment prior to IVF treatment avoids surgery and establishes a pregnancy rate comparable to a control group without fibroids.

PurposeTo determine whether concomitant tamoxifen 20 mg with gonadotropins (tamoxifen-gonadotropin) versus letrozole 5 mg with gonadotropins (letrozole-gonadotropin) affects mature oocyte yield.MethodsOpen-label, single-institution, randomized trial. Inclusion criteria included the following: females, ages 18–44 years old, with new diagnosis of non-metastatic breast cancer, who were undergoing fertility preservation with either oocyte or embryo cryopreservation. Those with estrogen-receptor-positive (ER+) breast cancer were randomized to tamoxifen-gonadotropin or letrozole-gonadotropin. Another group with estrogen-receptor-negative (ER−) breast cancer was recruited, as a prospectively collected comparison arm who took neither letrozole nor tamoxifen (gonadotropin only). The primary outcome was the number of mature oocytes obtained from the cycle. The randomized groups were powered to detect a difference of three or more mature oocytes.ResultsForty-five patients were randomized to tamoxifen-gonadotropin and fifty-one to letrozole-gonadotropin. Thirty-eight patients completed gonadotropin only. Age, antral follicle count, and body mass index were similar between the randomized groups. Our primary outcome of mature oocyte yield was similar between the tamoxifen-gonadotropin and letrozole-gonadotropin groups (12±8.6 vs. 11.6±7.5, p=0.81, 95%CI of difference =−2.9 to 3.7). In a pre-specified secondary comparison, mature oocyte yield was also similar with tamoxifen-gonadotropin or letrozole-gonadotropin versus gonadotropin only (12±8.6 vs. 11.6±7.5 vs. 12.4±7.2). There were no serious adverse events in any of the groups.ConclusionsTamoxifen-gonadotropin and letrozole-gonadotropin produced a similar number of mature oocytes. Women who received either tamoxifen-gonadotropin or letrozole-gonadotropin had a similar number of oocytes to the gonadotropin-only group.Trial registrationNCT03011684 (retrospectively registered 1/5/2017, after 9% enrolled)

Objective To optimize ovulation induction protocols for infertile women with PCOS, ovulation effect and adverse reactions of different doses of letrozole (2.5 vs 5.0 mg) combined sequentially HMG therapy were compared in infertility PCOS patients. Methods This open-label randomized controlled trial (RCT) included 174 infertile women aged 18–40 who met the Rotterdam criteria for PCOS at the Wuhan Union Hospital of China from May 2021 to January 2022. They were randomly assigned at a 1:1 ratio to 2.5 mg LE or 5.0 mg LE on cycle days 3–7 with sequential HMG injections ( n  = 87 for each). Results There is no difference in ovulation rate between LE (2.5 mg) + HMG group and LE (5.0 mg) + HMG group in infertile women with PCOS (85.1 vs 85.1%). The ongoing pregnancy rate was no different between the two groups (33.3 vs 25.3%). The percentage of type B endometrial tissues on HCG injection day was higher in the LE (2.5 mg) + HMG group (88.5% vs 69.0%). The monofollicular development rate was significantly higher in the LE (2.5 mg) + HMG group (67.8% vs. 46.0%). Conclusions Application of 5.0 mg LE followed with HMG does not improve the pregnancy rate compared to 2.5 mg LE in infertile women with PCOS. An increased dose of LE to 5.0 mg may increase the risks of OHSS and multiple pregnancies. Therapy of LE (2.5 mg) + HMG may be a more beneficial and optimal treatment protocol for improving endometrial receptivity and promoting mono-follicle development for patients with PCOS.

Background Mechanical endometrial injury prior to IVF has been suggested as a means to increase implantation rates by improving endometrial receptivity. However, the effects of endometrial injury in proliferative vs. luteal phase have not been studied before. This study aimed to explore whether endometrial injury in the proliferative phase of the preceding cycle before in vitro fertilization/embryo transfer (IVF-ET) improves the clinical outcomes in unselected subfertile women compared with injury in luteal phase. Methods A group of 142 patients who were good responders to hormonal stimulation were randomized into four groups: injury group (group A: endometrial injury in proliferative phase, n  = 38; group B: endometrium injury in luteal phase, n  = 32), and non-injury group as control (group C: non-injury in proliferative phase, n  = 36; group D: non-injury in luteal phase, n  = 36). Patients in injury groups underwent endometrial injury in either proliferative phase or luteal phase in the preceding cycle before IVF treatment. Clinical outcomes including implantation, pregnancy, and live birth rates were analyzed among the four groups. Results The baseline characteristics of the four groups including age, body mass index, duration, type and causes of infertility were similar. There were no significant differences in implantation, clinical pregnancy or live birth rates between injury group and non-injury group. Moreover, there were also no significant differences in implantation, clinical pregnancy, or live birth rates in injury in proliferative phase compared with luteal phase. Conclusions Endometrial injury in the cycle preceding IVF of unselected subfertile women does not increase implantation, clinical pregnancy, or live birth rates. Furthermore, there is no significant difference in clinical outcomes between endometrial injury in the proliferative phase and injury in the luteal phase. Trial registration This study was retrospectively registered on May 26th, 2017 (ChiCTR-IOR-17011506).

PurposeTo characterize the demographic differences between infertile/sub-fertile women who utilized infertility services vs. those that do not.MethodsA retrospective analysis of cross-sectional data obtained during the 2011–2013, 2013–2015, and 2015–2017 cycles of National Survey for Family Growth from interviews administered in home for randomly selected participants by a National Center of Health Statistics (NCHS) surveyor was used to analyze married, divorced, or women with long-term partners who reported difficulty having biological children (sub-fertile/infertile women). Demographic differences such as formal marital status, education, race, and religion were compared between women who presented for infertility care vs. those that did not. The primary outcome measure was presenting for infertility evaluation and subsequently utilizing infertility services. Healthcare utilization trends such as having a usual place of care and insurance status were also included as exposures of interest in the analysis.ResultsOf the 12,456 women included in the analysis 1770 (15.3%) had used infertility services and 1011 (8.3%) said it would be difficult for them to have a child but had not accessed infertility services. On univariate analysis, compared to women who used infertility services, untreated women had lower average household incomes (295.3 vs. 229.8% of the federal poverty line respectively). Untreated women also had lower levels of education and were more likely to be divorced or never have married. In terms of health status, unevaluated women were less likely to have a usual place for healthcare (87.3%) as compared to women presenting for fertility care (91.9%) (p = 0.004). When examining insurance status, 23.3% of unevaluated women were uninsured as compared to 8.3% of evaluated women. On multivariate analysis, infertile women without insurance were at 0.37 odds of utilizing infertility care compared to women with insurance.ConclusionsDemographic factors are associated with the utilization of infertility care. Insurance status is a significant predictor of whether or not infertile women will access treatment. Data from the three most recent NSFG surveys along with prior analyses demonstrate the need for expanded insurance coverage in order to address the socioeconomic disparities between infertile women who are accessing services vs. those that are not.