Analysis of PGT-M and PGT-SR outcomes at a Canadian fertility clinic.

OBJECTIVE: Outcomes from in vitro fertilization (IVF)/intrauterine insemination (ICSI) cycles for patients who underwent preimplantation genetic testing for monogenic/single gene (PGT-M) and structural chromosome rearrangements (PGT-SR) patients were reviewed. Patients pursuing PGT-M and PGT-SR often do not have pre-existing fertility issues and therefore may have uncertain expectations of successful outcomes. Before pursuing PGT-M and PGT-SR, patients require evidence-based counseling regarding the probability of having a healthy child. METHOD: Retrospective review from a single private IVF clinic of 73 PGT patients, from whom a total of 437 blastocysts were biopsied and screened. Embryo results and pregnancy outcomes were analyzed. RESULTS: Of the 45 PGT-M patients, 64.4% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 89.7%, with an ongoing pregnancy or delivery rate of 48.9%. For the 28 PGT-SR patients, 60.7% had at least one euploid unaffected embryo. The cumulative pregnancy rate for patients who had embryo transfers in this group was 87.5%, with an ongoing pregnancy or delivery rate of 42.9%. CONCLUSION: This information can supplement the existing data in the literature to counsel new patients in terms of realistic expectations of success following PGT-M and PGT-SR.

Frequencies of chromosome-specific mosaicisms in trophoectoderm biopsies detected by next-generation sequencing.

OBJECTIVE: To examine the chromosome-specific frequencies of mosaicism detected by next-generation sequencing (NGS) compared with constitutional aneuploidy. DESIGN: Retrospective cross-sectional review of NGS results from trophectoderm biopsies analyzed by per-chromosome prevalence of mosaicism and constitutional aneuploidy. SETTING: Private fertility clinic. PATIENT(S): A total of 378 patients who underwent preimplantation genetic screening by NGS for routine clinical indications from February 2016 to April 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Aneuploidies and mosaicisms were tabulated per chromosome, and whole-chromosome and segmental mosaicisms were also analyzed. RESULT(S): NGS results were analyzed from 1,547 blastocysts. Mosaicism was detected as the sole abnormality in 17.5% (n = 270) of samples but were also found in 196/634 aneuploid embryos, so the overall incidence of mosaicism per biopsy was 30.1%. Mosaicism did not statistically vary when stratified by maternal age. The mean rate of overall mosaicism per chromosome was 2.46%. When whole chromosome and segmental mosaicisms were compared, unequal frequencies were found in several chromosomes. Trisomy was more frequently detected as whole-chromosome mosaicism, although monosomy was more frequently seen in segmental mosaicism. Aneuploidy and mosaicism displayed different patterns of distribution in various chromosomes. CONCLUSION(S): Mosaicism is unequally detected in various chromosomes and appears distinct from the distribution pattern of constitutional aneuploidy. Whole chromosome and segmental mosaicisms are also differentially detected. These results contribute to the study of mosaicism, illuminating a differential pattern of detection across the genome.

Prevalence and Treatment Choices for Couples with Recurrent Pregnancy Loss Due to Structural Chromosomal Anomalies.

OBJECTIVE: Parental carriers of balanced structural chromosomal rearrangements such as reciprocal or Robertsonian translocations are at increased risk of recurrent pregnancy loss (RPL) due to the production of gametes with unbalanced non-viable chromosome variants. As a purported means of improving reproductive outcomes in this population, IVF and preimplantation genetic diagnosis (PGD) have been introduced as an alternative to natural conception and prenatal diagnosis. In this study, we evaluate the prevalence and treatment choices of couples with structural chromosomal rearrangement referred to a tertiary care RPL clinic. In addition, we compare the two methods of management in terms of live birth rate. METHODS: This is a retrospective chart review of 2321 couples who were referred to a highly specialized RPL clinic for ongoing clinical management between January 2005 and December 2013 (n = 23). Couples who pursued PGD through local fertility centres during this time were also included (n = 13). RESULTS: Thirty-six couples (1.6%) were found to be parental carriers of a structural chromosomal rearrangement. In this cohort, couples were twice as likely to pursue natural conception compared with IVF with PGD. No significant differences were observed in live birth rate between PGD and clinical management (66.6% vs. 53.3%, P = 0.717). With PGD management, six live birth outcomes were observed, with an incidence of one birth in 5.63 years of follow-up. With clinical management, 24 live birth outcomes were observed, with an incidence of one birth in 4.09 years of follow-up. Mean time to live birth was 17.5 months and 23.3 months in clinical management and PGD, respectively. CONCLUSIONS: Among couples presenting to a tertiary RPL clinic, parental carriers of structural chromosomal rearrangement and history of RPL are more likely to pursue natural conception over IVF and PGD. With regards to reproductive outcomes, no significant difference in miscarriage rate, time to live birth, or live birth rate was observed between couples who pursued PGD compared with expectant clinical management.

Should IVF be used as first-line treatment or as a last resort? A debate presented at the 2013 Canadian Fertility and Andrology Society meeting.

Infertility outcomes can be influenced by many factors. Although a number of treatments are offered, deciding which one to use first is a controversial topic. Although IVF may have superior efficacy in achieving a live birth with a reasonable safety profile, the availability of cheaper and less invasive treatments preclude its absolute use. For this reason, certain patient groups with 'good-prognosis' infertility are traditionally treated with less invasive treatments first. 'Good-prognosis' infertility may include unexplained infertility, mild male factor infertility, stage I or II endometriosis, unilateral tubal blockage and diminished ovarian reserve. Here, evidence behind the use of IVF as a first-line treatment is compared with its use as a last-resort option in women with 'good-prognosis' infertility.

Essure treatment of hydrosalpinges.

OBJECTIVE: To describe the use of Essure microinsert placement in patients with hydrosalpinges before IVF. DESIGN: Retrospective case-series. SETTING: An advanced endoscopic practice within a university-affiliated teaching hospital. PATIENT(S): Five women with unilateral or bilateral hydrosalpinges on transvaginal ultrasound, laparoscopy, or hysterosalpingogram who were planning further fertility therapy. In all patients, laparoscopy was felt to be relatively contraindicated because of previous extensive abdominopelvic surgery. INTERVENTION(S): Hysteroscopic placement of the Essure microinsert in four patients under general anesthesia. One patient underwent fluoroscopically guided placement. MAIN OUTCOME MEASURE(S): Placement rates and postoperative recovery, technical challenges in Essure placement, and results of subsequent treatment with IVF when available. RESULT(S): Successful bilateral Essure placement was confirmed in two of five patients. Unilateral placement was achieved in two of five. There were no postoperative complications. No pregnancies have occurred thus far. CONCLUSION(S): Hysteroscopic placement of the Essure microinsert is a minimally invasive option for proximal tubal occlusion. In patients requiring occlusion of hydrosalpinges before IVF and with contraindications to abdominal surgery, this technique may offer a safer alternative. Preoperative documentation of proximal tubal patency helps predict placement success. Further research into this unique clinical scenario is required.

A follow-up study of women who donated oocytes to known recipient couples for altruistic reasons.

BACKGROUND: Current legislation in Canada allows for only altruistic gamete donation. Limited clinical data are available on the emotional and psychological impact of altruistic oocyte donation on known donors. METHODS: Seventeen women who had donated oocytes to known parties without financial compensation agreed to receive the oocyte donation questionnaire (ODQ) to explore the psychological domains of altruistic oocyte donation. RESULTS: Thirteen ODQ were returned, giving a response rate of 76%. All subjects indicated that they were primarily motivated by a 'desire to give and help' the recipient couple. Most subjects did not find the donation decision difficult but some found the post-donation psychological adjustments challenging. Subjects also indicated that mandatory counselling on the psychological implications of oocyte donation was an important component of cycle preparation. The majority of subjects had disclosed the donation to others and felt that disclosure to the presumptive child was essential. CONCLUSIONS: The findings provide clinical materials for conceptualizing the dynamics entailed by known altruistic oocyte donation, with regards to motivation, relationship implications, donor satisfaction and plans for disclosure. The data support the provision of psycho-social support services to help donors dealing with any residual emotional difficulties regardless of the outcome of oocyte donation.

Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate.

OBJECTIVE: To evaluate the incidence of congenital malformations among offspring of mothers who conceived with clomiphene citrate (CC) or with letrozole treatment for infertility. DESIGN: Retrospective study. SETTING: 5 fertility centers in Canada. PATIENTS: 911 newborns from women who conceived following CC or letrozole treatment. INTERVENTIONS: Examination of medical files of both mother and newborn, and cross-checked with the parents by telephone calls. MAIN OUTCOME MEASURES: Identified major and minor congenital malformations, birth weight, age of the mother, and type of treatment that led to the conception. RESULTS: Overall, congenital malformations and chromosomal abnormalities were found in 14 of 514 newborns in the letrozole group (2.4%) and in 19 of 397 newborns in the CC group (4.8%). The major malformation rate in the letrozole group was 1.2% (6/514) and in the CC group was 3.0% (12/397). One newborn in the letrozole group was found to have a ventricular septal defect (0.2%) compared to 4 newborns in the CC group (1.0%). In addition, the rate of all congenital cardiac anomalies was significantly higher (P: 0.02) in the CC group (1.8%) compared to the letrozole group (0.2%). CONCLUSION: There was no difference in the overall rates of major and minor congenital malformations among newborns from mothers who conceived after letrozole or CC treatments. However, it appears that congenital cardiac anomaly is less frequent in the letrozole group. The concern that letrozole use for ovulation induction could be teratogenic is unfounded based on our data.

Activated protein C and the ovarian hyperstimulation syndrome: possible therapeutic implications.

Given the efficacy and safety of recombinant human activated protein C (rhAPC) in the systemic inflammatory response syndrome (SIRS), this study was designed to review the evidence for rhAPC as a possible therapeutic option in the treatment of severe ovarian hyperstimulation syndrome (OHSS). SIRS, like OHSS, is a proinflammatory and prothrombotic disorder whose cornerstone is endothelial dysfunction in which protein C deficiency is a frequent occurrence. Recently, the use of rhAPC has been shown to be of benefit with a reduction in mortality and an improvement in indicators of inflammation and coagulation. OHSS is typically an iatrogenic disorder resulting from ovarian stimulation as a component of infertility treatment. The pathogenesis of OHSS, like sepsis, is related to endothelial dysfunction and inflammation and can result in significant morbidity including end organ hypoperfusion, disseminated intravascular coagulation (DIC), thrombosis, and occasionally, death. We have performed a review of the literature to identify similarities between these disease processes to develop a theoretical basis for the use of rhAPC in patients with moderate to severe OHSS. Use of rhAPC in this group may attenuate the disease process and reduce the potential morbidity associated with this iatrogenic disorder.