Noninvasive Endometrial Receptivity Prediction

The main objective of this study was to establish a prediction tool for endometrial receptivity using transcriptome sequencing data and to evaluate the feasibility of a noninvasive endometrial receptivity test using uterine fluid specimens. First, from November 2017 to December 2018, participants were recruited for us to identify differentially expressed genes (DEGs) in pre-receptive, receptive and post-receptive uterine fluid by transcriptome sequencing and expression profile analysis and to build the nirsERT model applying a random forest (RF) machine learning algorithm. To limit interference from confounding variables affecting ER, the inclusion criteria for IVF patients were set as follows: 20–39 years of age; body mass index (BMI) = 18–25 kg/m2; patients with a history of a intrauterine pregnancy/pregnancies who underwent the first IVF cycle due to tubal factors alone or patients who undergoing the first IVF cycle due to male factors alone; a regular menstrual cycle length (25–35 days) with spontaneous ovulation; normal ovarian reserves (baseline FSH < 10 mIU/mL, antimullerian hormone > 1.5 ng/ml, and antral follicle count > 5); able to be followed up to assess the pregnancy outcome; and successful intrauterine pregnancy after the first embryo transfer (ET). Intrauterine pregnancy was defined as the presence of a gestational sac with or without fetal heart activity in the uterine cavity as evaluated by ultrasound 4–5 weeks after ET. To establish the prediction tool, normal ER status was defined as a successful intrauterine pregnancy.
Second, from January to April 2019, participants were recruited to demonstrate the accuracy of the nirsERT in predicting the WOI. The inclusion criteria for patients from which we collected uterine fluid on the day of cryothaw blastocyst transfer were as follows: 20–39 years of age; BMI = 18–25 kg/m²; ultrasound showing an endometrial thickness of ≥8 cm and an endogenous serum progesterone level of ≤1.2 ng/ml on the day of progesterone administration/LH peak; and transferred embryos with high-quality blastocysts (blastocysts ≥3 BB on Day 5 and Day 6, graded based on the Gardner system) [29 (link)].
The following exclusion criteria were applied: endometrial diseases (including intrauterine adhesions, endometrial polyps, endometritis, endometrial tuberculosis, endometrial hyperplasia, and a thin endometrium); hydrosalpinx without proximal tubal ligation; submucous myomas, intramural hysteromyomas, or adenomyomas protruding toward the uterine cavity; endometriosis (stages III–IV); uterine malformations; and other medical or surgical comorbidities identified by consulting medical records, physical examination, blood tests, B-ultrasound and X-ray examination.
In the validation group, all patients received the nirsERT and were followed up to 4–5 weeks after ET to determine intrauterine pregnancy by ultrasound. Subsequently, all patients diagnosed with an intrauterine pregnancy were followed up until delivery.