Integrated treatment guided by RNA-seq-based endometrial receptivity assessment for infertility complicated by MEN1.

Background: Preimplantation genetic testing (PGT) serves as a tool to avoid genetic disorders in patients with known genetic conditions. However, once a selected embryo is transferred, implantation success is attained independent of embryo quality. Using PGT alone is unable to tackle implantation failure caused by endometrial receptivity (ER) abnormalities in these patients. Methods: We validated our newly developed RNA-seq-based ER test (rsERT) in a retrospective cohort study including 511 PGT cycles and reported experience in treating an infertile female patient complicated by multiple endocrine neoplasia type 1 (MEN1). Results: Significant improvement in the clinical pregnancy rate was found in the performed personalized embryo transfer (pET) group (CR, 69.7%; P = 0.035). In the rare MEN1 case, pET was done according to the prediction of the optimal time of window of implantation after unaffected blastocysts were obtained by PGT-M, which ultimately led to a healthy live birth. However, none of the mRNA variants identified in the patient showed a strong association with the MEN1 gene. Conclusions: Applying the new rsERT along with PGT improved ART outcomes and brought awareness of the importance of the ER examination in MEN1 infertile female patients. MEN1-induced endocrine disorder rather than MEN1 mutation contributes to the ER abnormality. Trial Registration: Reproductive Medicine Ethics Committee of Xiangya Hospital Registry No.: 2022010.

An endometrium of type C along with an endometrial thickness of < 8 mm are risk factors for ectopic pregnancy after stimulated cycles with fresh embryo transfer.

BACKGROUND: The study investigated whether specific ultrasonographically observed endometrial features (including endometrium type and thickness) were linked to ectopic pregnancy after stimulated cycles with fresh embryo transfer. METHOD: Of 6246 pregnancy cycles after fresh embryo transfer, 6076 resulted in intrauterine pregnancy and 170 in ectopic pregnancy. The primary outcome of the study was ectopic pregnancy, with the main variables being endometrium type and endometrial thickness. Univariate and subsequent multiple-stepwise logistic regression analyses were used to identify the risk factors of ectopic pregnancy. RESULTS: 1. Compared with patients with an endometrial thickness ≥ 8 mm, the adjusted odds ratio for those with an endometrial thickness < 8 mm was 3.368 (P < 0.001). The adjusted odds ratio for women with a type-C endometrium was 1.897 (P = 0.019) compared with non-type C. 2. A larger dose of gonadotropin used during controlled ovarian hyperstimulation was a protective factor against ectopic pregnancy (P = 0.008). 3. The GnRH antagonist protocol (P = 0.007) was a risk factor for ectopic pregnancy, compared with the use of GnRH agonists. CONCLUSION: (1) An endometrial thickness < 8 mm coupled with a type C endometrium significantly increased the risk of ectopic pregnancy after fresh embryo transfer. (2) A thin endometrial thickness and a type C endometrium could be further related to an abnormal endometrial receptivity/peristaltic wave. (3) Patients at a high risk of ectopic pregnancy should therefore be given special attention, with early diagnosis during the peri-transplantation period may assist in the prevention of ectopic pregnancy.

An Endometrial Thickness < 8 mm Was Associated With a Significantly Increased Risk of EP After Freeze-Thaw Transfer: An Analysis of 5,960 Pregnancy Cycles.

Introduction: Endometrium characteristics that are most likely to induce ectopic pregnancy were investigated on the basis of the data of 5,960 pregnant freeze-thaw cycles. Methods: A total of 5,960 pregnancy cycles after freeze-thaw embryos transfer were included, with the number of intrauterine and ectopic pregnancies being 5,777 and 183, respectively. Ectopic pregnancy was the primary outcome. Endometrial thickness was the main measured variable. The risk factors of ectopic pregnancy were eventually determined based on univariate analysis and subsequent multiple-stepwise logistic regression analysis. Results: 1. After adjusting for confounders, endometrial thickness could independently predict ectopic pregnancy. The adjusted odd ratios for women with endometrial thickness in the ranges of < 8 mm, 8-9.9 mm, and 10-11.9 mm were 3.270 [95% confidence interval (CI), 1.113-9.605, P = 0.031], 2.758 (95% CI, 0.987-7.707, P = 0.053), and 1.456 (95% CI, 0.502-4.225, P = 0.489), respectively, when compared with those having an endometrial thickness of 12-13.9 mm. 2. Endometrial type and preparation protocol were however not identified as risk factors for ectopic pregnancy. Discussion: 1. After freeze-thaw embryo transfer, risks of ectopic pregnancy were significantly higher when the endometrial thickness was < 8 mm. 2. A thin endometrial thickness could be linked with abnormal endometrial peristaltic waves or abnormal endometrial receptivity. 3. Adequate attention should therefore be paid to patients with a thin endometrial thickness to prevent EP or to achieve early diagnosis during the peri-transplantation period.

Correction to: Value of endometrial echo pattern transformation after hCG trigger in predicting IVF pregnancy outcome: a prospective cohort study.

An amendment to this paper has been published and can be accessed via the original article.

Value of endometrial echo pattern transformation after hCG trigger in predicting IVF pregnancy outcome: a prospective cohort study.

BACKGROUND: There is much value in identifying non-invasive ways of measuring endometrial receptivity, as it has the potential to improve outcomes following in vitro fertilization (IVF). It has been suggested that endometrial echogenicity on the day of hCG administration was a good marker of endometrial receptivity. In the daily practice, we notice that patients with non-homogeneous hyperechoic endometrium on the embryo transfer day usually have lower pregnancy rates. We therefore extended the research onward transformation of echo pattern after hCG trigger to analyze the relationship between endometrial echogenicity transformation and IVF outcomes. METHODS: A total of 146 infertile women undergoing their first IVF cycle were recruited in the prospective cohort study from August 2017 through August 2018. A series of endometrial echo pattern monitoring was carried out in these patients after hCG trigger: hCG day, from 1 through 3 days after ovum pick-up (OPU + 1, OPU + 2, OPU + 3). RESULTS: The endometrial echogenicity value was calculated as the ratio of the hyperechogenic endometrial area over the whole endometrial area. Clinical pregnancy rate and embryo implantation rate had positive relationship with echogenicity value. The ROC curve analysis of endometrial echogenicity showed the area under curve was greatest on the second day after oocyte retrieval (OPU + 1, 2, 3 were 0.738, 0.765, 0.714 respectively) versus pregnancy. Endometrial echogenicity value on OPU + 2 had a higher predictive efficiency, and the cutoff value was 76.5%. The sensitivity was 61.3% and specificity was 82.0%. When putting the cut-off at <60%, the sensitivity was 93.8% and the specificity was 23.1%. CONCLUSIONS: The endometrial echogenicity value on OPU + 2 was recommended to evaluate endometrial receptivity. It seemed appropriate for clinicians to provide a 'freeze all' IVF cycle and transfer in a subsequent frozen-thawed embryos cycle when echogenicity value <60% on OPU + 2. TRIAL REGISTRATION: The registration number was ChiCTR-OOC-17012214 and the registration date was August 1st, 2017.

Inhibition of endometrial fundocervical wave by phloroglucinol and the outcome of in vitro fertilization.

One hundred thirty-five infertile patients were enrolled to investigate the efficacy of phloroglucinol-induced inhibition of the endometrial fundocervical wave and its effect on in vitro fertilization (IVF). We found that phloroglucinol significantly inhibited (P<0.05) peristaltic fundocervical wave, suggesting a feasible way of application of phloroglucinol to suppress endometrial waves during IVF.

Influence of controlled ovarian hyperstimulation on uterine peristalsis in infertile women.

STUDY QUESTION: Is there a difference in the characteristics of uterine peristalsis in natural and controlled ovarian hyperstimulation (COH) cycles? SUMMARY ANSWER: COH significantly changed the uterine peristaltic pattern. WHAT IS KNOWN ALREADY: In natural menstrual cycles, the periodic changes of uterine peristalsis are closely related to the reproductive process. STUDY DESIGN, SIZE, DURATION: This is a prospective cohort study with a total of 64 subjects involved. The study was performed between May 2011 and August 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixty-four infertile women with regular, ovulatory menstrual cycles underwent follicular tracking in one natural cycle and after ovarian stimulation (GnRH-agonist down-regulation) in the subsequent cycle (COH). Three time points were studied in both cycles: at LH surge/HCG plus 1 day, ovulation/oocyte retrieval and 2 days after ovulation/retrieval. The study was performed in an IVF center of the university-affiliated Xiangya hospital. MAIN RESULTS AND THE ROLE OF CHANCE: Uterine peristaltic wave frequency was 1.31 times higher in the COH than in the natural cycle (P< 0.01). At all three time points in the COH cycle, waves moving from the cervix to fundus dominated, comprising 80-90% of the wave types observed, while 'no activity' was more frequently observed in the natural cycle. The wave frequency was positively correlated with the level of serum estradiol (E(2)) (r= 0.30; P< 0.01) and negatively correlated with the progesterone level (r= -0.48; P< 0.01) for the physiological range of steroid levels. No correlation was found between the wave frequency and supraphysiological concentrations of E(2) or progesterone. LIMITATIONS, REASONS FOR CAUTION: The two observers were not independent and this was a limitation of the study. Quantitative measurements of wave amplitude in the different cycles should be compared in future research. WIDER IMPLICATIONS OF THE FINDINGS: Uterine peristalsis was much higher in the COH cycle than in the natural cycle. The endometrial movements did not weaken to the natural level before embryo transfer, even with high levels of progesterone. The wave frequency was positively correlated with serum E(2) level and negatively correlated with that of progesterone within the physiological range. No correlation was found between the wave frequency and supraphysiological concentrations of E(2) and progesterone.