Prenatal cell-free DNA screening for chromosomal aneuploidies after euploid embryo transfer shows high concordance with PGT-A results and low positive predictive values.

OBJECTIVE: To evaluate the positive predictive value (PPV) of prenatal cell-free DNA screening for chromosomal aneuploidies in pregnancies achieved either after single euploid transfer in IVF/PGT cycles or transfer of single untested embryo, and to assess the concordance of prenatal-cfDNA-screening and PGT-A results. DESIGN: Single centre retrospective cohort study SUBJECTS: 2973 prenatal-cfDNA-screening results for the most common trisomies(T)(T13,T18,T21,X,Y) and microdeletions(1p36;4p16.3;5p15.2;15q11.2;22q11.2) from singleton pregnancies allocated into 2 groups: PGT-A group (n=1204) pregnancy after single euploid transfer and non-PGT-A group (n=1769) pregnancy after transfer of single untested embryo, between 2016 and 2023. MAIN OUTCOME MEASURES: Primary outcome measure was accuracy of prenatal-cell-free-DNA-screening. Positive and negative prenatal-cell-free-DNA-screening results, and subsequent prenatal or postnatal diagnostic testing were used to classify each positive prenatal-cell-free-DNA-screening result as a true or a false positive. Secondary endpoints were to evaluate the concordance of PGT-A and prenatal-cell-free-DNA-screening results and to assess the differences of the fetal fraction of cell-free-DNA used for prenatal-cell-free-DNA-screening report between the study groups. RESULTS: Prenatal-cell-free-DNA-screening was performed at mean 11.3±1.8weeks gestational age (GA) and yielded results in 99.9% of the patients (0.1% cancellation rate). There was no difference in the fetal fraction between PGT-A tested and not tested pregnancies (9.5%±4% vs 10.3%±4%). 13 positive prenatal-cell-free-DNA-screening results (2-T21,2-X0,4-XXX,1-XYY, 1-indeterminate sex, 2-22q11 del/dup, 1-15q11.2) were received for PGT-A group. Only one (22q11 dup) was confirmed with amniocentesis and fetal autopsy, giving a PPV for an abnormal prenatal-cfDNA-screening of 7.7%, the rest had results concordant with PGT-A. Sex chromosomes were 100% concordant between prenatal-cell-free-DNA-screening and PGT-A results, giving a 100% PPV for PGT-A for sex chromosomes and 100% NPV for aneuploidies. Positive prenatal-cell-free-DNA-screening results were received for 27 pregnancies from untested embryos (1.5%), follow up testing was electively performed for 21, and 8 had confirmed the prenatal-cell-free-DNA-screening result, giving a PPV for the non-PGT-A group of 38%. CONCLUSION: This study demonstrates that patients undergoing IVF/PGT and single euploid embryo transfer can reliably do prenatal-cell-free-DNA-screening during their first trimester. Fetal fraction in singleton pregnancies after PGT-A tested embryos is not different from pregnancies with untested embryos. PPV for an abnormal prenatal-cell-free-DNA-screening result after euploid embryo transfer was reassuringly low (7.7%). PGT-A reliably selects against aneuploidy with 100% concordance with fetal sex.

Safety and Assisted Reproductive Technology Outcomes of Hysteroscopic Tubal Microinserts Versus Laparoscopic Proximal Tubal Occlusion or Salpingectomy for Hydrosalpinges Treatment.

OBJECTIVE: This study sought to answer the following question: What are the complications and assisted reproductive technology outcomes among women with hydrosalpinges managed by hysteroscopic microinsert tubal occlusion compared with women with hydrosalpinges managed by laparoscopic proximal tubal occlusion or salpingectomy? METHODS: This was a retrospective cohort study conducted from January 2009 to December 2014 at two academic, tertiary care, in vitro fertilization centres in Toronto, Ontario. All patients (n = 52) who underwent hysteroscopic tubal occlusion for hydrosalpinges were identified. Patients who proceeded with embryo transfer cycles after hysteroscopic microinsert (n = 33) were further age matched to a cohort of patients who underwent embryo transfer after laparoscopic proximal tubal occlusion or salpingectomy (n = 33). Main outcome measures were clinical pregnancy rate per patient and per embryo transfer cycle. RESULTS: Among 33 patients, there were 39 fresh and 37 frozen embryo transfer cycles in the hysteroscopic group (group A); among 33 patients in the laparoscopic group (group B), there were 42 fresh and 29 frozen embryo transfer cycles. The cumulative clinical pregnancy rate in group A and group B was similar (66.7% vs. 69.7%, respectively; P = 0.8). The clinical pregnancy rate per embryo transfer cycle was also similar in both groups (28.9% in group A vs. 32.4% in group B; P = 0.6). There were two incidents of ectopic pregnancy in the laparoscopic group and no ectopic pregnancy in the hysteroscopic group. There were three major complications: tubo-ovarian abscess, distal migration of the coil after microinsert placement, and an acute abdomen following the hysteroscopic procedure. CONCLUSION: Pregnancy outcomes after hysteroscopic placement of a microinsert for hydrosalpinx management before embryo transfer were comparable to those following laparoscopic proximal tubal occlusion or salpingectomy. However, caution is advised regarding microinsert placement for hydrosalpinges before proceeding with assisted reproductive technology.

In Vitro Fertilization Success Rates after Surgically Treated Endometriosis and Effect of Time Interval between Surgery and In Vitro Fertilization.

STUDY OBJECTIVE: To evaluate the impact of endometriosis staging and endometriomas on in vitro fertilization (IVF) outcome and to assess the optimal time interval between laparoscopy and IVF. DESIGN: A retrospective clinical study (Canadian Task Force classification II1). SETTING: A university-affiliated private infertility clinic. PATIENTS: Two hundred sixteen infertile patients with endometriosis and 209 infertile patients without endometriosis. INTERVENTIONS: Laparoscopy, IVF. MEASUREMENTS AND MAIN RESULTS: Patients with endometriosis were classified according to American Society for Reproductive Medicine criteria; 58, 67, 63, and 28 patients had stages 1 through 4 disease, respectively. Patients with endometriosis had significantly lower estradiol on trigger day (9986 ± 6710 vs 12 220 ± 9414 pg/mL, respectively) and number of retrieved oocytes (12.7 ± 8.6 vs 14.0 ± 10, respectively) compared with controls. We found a consistent decline in clinical and ongoing pregnancy rates with increasing stage of endometriosis. The presence of endometrioma in patients with stages 3 and 4 endometriosis did not alter IVF outcome. Patients with a time interval of 7 to 12 and 13 to 25 months after surgery had a favorable outcome. CONCLUSION: IVF pregnancy rate was negatively correlated with endometriosis severity. The presence of endometriomas had no impact on IVF clinical outcome. The optimal time to perform IVF appears to be between 7 and 25 months after endometriosis surgery.

Significant correlation between anti-müllerian hormone and embryo euploidy in a subpopulation of infertile patients.

Anti-Müllerian hormone (AMH) is a standard marker of ovarian reserve. Correlation between AMH and egg euploidy is controversial. We evaluated the association between AMH and blastocyst euploidy rate examined by pre-implantation genetic screening (PGS). This retrospective study was conducted at the CReATe Fertility Centre. We included single IVF cycles of 216 infertile couples, which resulted in 911 blastocysts subjected to array comparative genomic hybridization and evaluated IVF outcome after embryo transfer. The average age and median AMH of female patients were 37.2 (SD = 3.8) and 20 pmol/l, respectively, and the average euploidy rate was 38.3%. Using multivariate regression controlling for age, antral follicle count, body mass index and parity, there was a significant association between serum AMH and proportion of euploid embryos (P = 0.02), due to the dominant ≤36 age group in which significant correlation between AMH and euploidy rate (P = 0.02) was demonstrated. Clinical outcome was similar, including biochemical, clinical and ongoing pregnancy rates as well as pregnancy loss. This study shows a correlation between AMH and aneuploidy rate, specifically among infertile patients younger than 37 years old. Study limitations are discussed.

Lower complication rates with office-based D&C under ultrasound guidance for missed abortion.

BACKGROUND: Missed abortion (MA) can be managed expectantly, medically or surgically. Surgical management has been performed safely in the office setting by suction dilation and curettage (D&C). Prior studies suggest that intraoperative ultrasound guidance (USG) may reduce complications for first-trimester therapeutic abortion. The aim of this study was to evaluate the safety of office D&C for MA using real-time USG. METHODS: This retrospective cohort study included 255 patients who underwent office D&C under USG for first trimester MA at a single university-affiliated fertility clinic during January 2011-December 2013. Transabdominal USG was utilized during the procedure and was immediately followed by a transvaginal ultrasound examination to confirm full evacuation. Intra- and postoperative complication rates were compared to previously published data. RESULTS: There were no intraoperative complications, including excessive blood loss or uterine perforation. Two of the 255 patients (0.87%) were diagnosed with RPOCs requiring uterine re-evacuation. This rate of RPOCs was superior to rates previously reported for D&Cs without USG (2.6-4.9%, P=0.046). There were no other post procedure complications identified. CONCLUSIONS: We observed very low complications rate in Office-based D&C under USG, lower than those reported in the literature with unguided D&C.

Comparison of IVF Outcomes between Minimal Stimulation and High-Dose Stimulation for Patients with Poor Ovarian Reserve.

We examined whether treatment with minimum-dose stimulation (MS) protocol enhances clinical pregnancy rates compared to high-dose stimulation (HS) protocol. A retrospective cohort study was performed comparing IVF and pregnancy outcomes between MS and HS gonadotropin-antagonist protocol for patients with poor ovarian reserve (POR). Inclusion criteria included patients with an anti-Müllerian hormone (AMH) ≤8 pmol/L and/or antral follicle count (AFC) ≤5 on days 2-3 of the cycle. Patients from 2008 exclusively had a HS protocol treatment, while patients in 2010 had treatment with a MS protocol exclusively. The MS protocol involved letrozole at 2.5 mg over 5 days, starting from day 2, overlapping with gonadotropins, starting from the third day of letrozole at 150 units daily. GnRH antagonist was introduced once one or more follicles reached 14 mm or larger. The HS group received gonadotropins (≥300 IU/day) throughout their antagonist cycle. Clinical pregnancy rate was significantly higher in the MS protocol compared to the HS protocol (P = 0.007). Furthermore, the live birth rate was significantly higher in the MS group compare to the HS group (P = 0.034). In conclusion, the MS IVF protocol is less expensive (lower gonadotropin dosage) and resulted in a higher clinical pregnancy rate and live birth rate than a HS protocol for poor responders.