Publications by authors named "Robert Casper"

181 Publications

Cleavage vs blastocyst stage embryos: how are they interrelating?

Arch Gynecol Obstet 2021 Feb 23. Epub 2021 Feb 23.

IVF Unit, Department of Obstetrics and Gynecology, Sackler Faculty of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, Tel Aviv University, Tel Aviv, Israel.

Purpose: To assess the variables that may predict which cleavage-stage embryo may develop into a blastocyst, and vice versa, to determine whether the cleavage-stage embryo morphology should be taken into consideration when transferring the embryo at the blastocyst stage.

Methods: A single center, retrospective cohort study. The study cohort included 3072 patients undergoing 3607 retrieval cycles and 23,124 embryos at the cleavage stage. We assessed the blastulation rate and evaluated which variables impact the ongoing pregnancy rate.

Results: High blastulation rate correlates with higher embryos' grading (I > II > III > IV > V) and higher number of blastomeres (8 > 7 > 6 > 5 > 4). 949 patients had fresh single blastocyst transfers. The ongoing pregnancy rate was 28.9% per transfer. Patients with ongoing pregnancies were significantly younger (34.3 vs. 36 years, p < 0.001), had higher number of oocyte yield (9.8 vs. 9, p = 0.02), and an increased rate of good-quality embryos transferred (70.7% vs. 47.7%, p = 0.001). When evaluating embryos progression, we found that whenever embryo developed to a good-quality blastocyst, its appearance at the cleavage stage did not affect ongoing pregnancy rate.

Conclusion: Higher the number of blastomeres and better embryo grading were found to correlate with a higher blastulation rate. Nevertheless, if the embryo has already developed to a top-quality blastocyst, its morphology at the cleavage stage did not impact ongoing pregnancy rate.
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http://dx.doi.org/10.1007/s00404-021-06003-zDOI Listing
February 2021

Low risk of OHSS with follitropin delta use in women with different polycystic ovary syndrome phenotypes: a retrospective case series.

J Ovarian Res 2021 Feb 12;14(1):31. Epub 2021 Feb 12.

TRIO Fertility, and Department of Obstetrics and Gynecology, University of Toronto, 655 Bay St, Suite 1101, Toronto, ON, M5G2K4, Canada.

Background: To explore the efficacy of follitropin delta in ovarian stimulation of patients with the Rotterdam ESHRE/ASRM 2003 phenotypes of polycystic ovarian syndrome (PCOS) using a retrospective case series with an electronic file search in a reproductive medicine clinic.

Case Presentation: Seventy-four patients with PCOS undergoing ovarian stimulation according to the individualized dosing algorithm of follitropin delta for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI)/oocyte freezing were included. Follitropin delta resulted in a high number of pre-ovulatory follicles at the end of stimulation as expected in patients with PCOS. There was a large number of oocytes retrieved with an acceptable percentage of metaphase II (MII) oocytes. There were no cases of moderate or severe OHSS across all phenotypes.

Conclusion: Follitropin delta, using the individualized dosing algorithm, appears to be a safe method of ovarian stimulation with a low risk of OHSS in PCOS patients without sacrificing successful stimulation outcomes.
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http://dx.doi.org/10.1186/s13048-021-00773-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881448PMC
February 2021

Prise en charge des fibromes utérins après le retrait de Fibristal du marché.

J Obstet Gynaecol Can 2021 Jan 23. Epub 2021 Jan 23.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON.

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http://dx.doi.org/10.1016/j.jogc.2021.01.012DOI Listing
January 2021

Can Oocyte Diameter Predict Embryo Quality?

Reprod Sci 2021 Mar 2;28(3):904-908. Epub 2020 Sep 2.

TRIO Fertility Partners, Division of Reproductive Sciences, University of Toronto, 655 Bay St 11th floor, Toronto, ON, M5G 2K4, Canada.

With the recent increased utilization of oocyte vitrification for the purpose of fertility preservation, information regarding the future fertility potential of the frozen oocytes is mandatory. Nowadays, there is a relative lack of data about prediction of assisted reproductive technique (ART) success relying on the retrieved oocytes. In the present study, we therefore aimed to investigate whether oocyte diameter might predict the quality of the developing embryo. A retrospective, single-center cohort study. Oocytes retrieved following controlled ovarian hyperstimulation cycles during 2016 and incubated in a time-lapse incubator system were analyzed. Oocytes were grouped by mean oocyte diameter (MOD) and incubated for 5 days before the final morphological evaluation done by an expert embryologist. A total of 471 cycles which yielded 3355 metaphase II oocytes were included in the analysis. Embryos developed from oocytes with MOD close to the average (Average 1SD < MOD < Average + 1SD) had increased good-quality blastulation rates compared with embryos that developed from very small or very large oocytes. Oocytes with MOD between 105.96 and 118.69 μm have better probability of becoming top-quality D5 blastocysts (17.1-17.4% grade 1 embryos). There is a correlation between oocyte's MOD and the embryo quality at day 5. The oocytes with near average MOD have a better chance to develop to a good-quality embryo. Therefore, the study suggests that MOD might serve as a predictor for embryo grading at day 5.
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http://dx.doi.org/10.1007/s43032-020-00306-3DOI Listing
March 2021

A battery boost for old eggs?

Authors:
Robert F Casper

Fertil Steril 2020 08 1;114(2):265-266. Epub 2020 Jul 1.

TRIO Fertility, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, and University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.fertnstert.2020.05.009DOI Listing
August 2020

Endometrial compaction before frozen euploid embryo transfer improves ongoing pregnancy rates.

Fertil Steril 2020 05;113(5):990-995

TRIO Fertility, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. Electronic address:

Objective: To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs).

Design: An observational cohort study.

Setting: Single tertiary care medical center.

Patient(s): Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post-preimplantation genetic testing for aneuploidy (PGT-A).

Intervention(s): Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET.

Main Outcome Measure(s): Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET.

Result(s): We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact.

Conclusion(s): There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant.
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http://dx.doi.org/10.1016/j.fertnstert.2019.12.030DOI Listing
May 2020

Frozen embryo transfer: evidence-based markers for successful endometrial preparation.

Authors:
Robert F Casper

Fertil Steril 2020 02;113(2):248-251

Division of Reproductive Sciences, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Health System; and TRIO Fertility, Toronto, Ontario, Canada. Electronic address:

Endometrial receptivity appears to be as important as chromosomal normality in determining embryo implantation and pregnancy outcome, because the ongoing pregnancy rate with transfer of preimplantation genetic testing for aneuploidy euploid blastocysts is ∼50%. This Views and Reviews article focuses on our current knowledge of the biology of endometrial receptivity and on the role of both invasive (endometrial biopsy) and noninvasive (ultrasound) assessment in successful endometrial preparation for frozen-thawed embryo transfer.
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http://dx.doi.org/10.1016/j.fertnstert.2019.12.008DOI Listing
February 2020

The Affordability and Accessibility of Ontario's Publicly Funded IVF Program: A Survey of Patients.

J Obstet Gynaecol Can 2020 05 13;42(5):568-575. Epub 2019 Dec 13.

TRIO Fertility, Toronto, ON; Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON.

Objective: On December 21, 2015, the Province of Ontario created the Ontario Fertility Program to fund one cycle of in vitro fertilization (IVF) to improve IVF affordability and access for Ontarians below age 43. The objective of this study was to determine whether the Program was meeting this goal, based on the experiences of participating patients.

Methods: Participation in an electronic survey was invited through posters and brochures placed within the waiting rooms of all 25 IVF clinics providing funded IVF in Ontario and by a survey link placed on websites focused on fertility issues.

Results: The survey was carried out at the end of the second year of the Program (September to December 2017), with 514 participants completing >75% of it. Program strengths were noted as follows: decreases in financial inequities of family building for the infertile; lowering of the opportunity cost of accessing IVF; and destigmatizing and raising public awareness of infertility as a legitimate medical condition. Weaknesses were as follows: lack transparency and consistency in clinics' patient prioritization schemes; clinic concentration in cities leading to geographic inequities in access; and high ancillary costs being financially burdensome. The following opportunities were suggested: funding of more than one IVF cycle and its supporting medications; standardization of prioritization schemes; and tying Program access to means testing.

Conclusion: Patients strongly support the Program and noted improved IVF affordability, but the Program's reliance on existing private clinics for treatment provision has meant unresolved geographic inequities and inconsistent prioritization schemes. Because this is the first Program study of patients' experience, the results will help policymakers determine areas to re-evaluate for continued or increased funding and opportunities to collaborate with health care providers and clinic owners to improve provision and access.
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http://dx.doi.org/10.1016/j.jogc.2019.09.024DOI Listing
May 2020

Removing Short Wavelengths From Polychromatic White Light Attenuates Circadian Phase Resetting in Rats.

Front Neurosci 2019 10;13:954. Epub 2019 Sep 10.

Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, United States.

Visible light is the principal stimulus for resetting the mammalian central circadian pacemaker. Circadian phase resetting is most sensitive to short-wavelength (blue) visible light. We examined the effects of removing short-wavelengths < 500 nm from polychromatic white light using optical filters on circadian phase resetting in rats. Under high irradiance conditions, both long- (7 h) and short- (1 h) duration short-wavelength filtered (< 500 nm) light exposure attenuated phase-delay shifts in locomotor activity rhythms by (∼40-50%) as compared to unfiltered light exposure. However, there was no attenuation in phase resetting under low irradiance conditions. Additionally, the reduction in phase-delay shifts corresponded to regionally specific attenuation in molecular markers of pacemaker activation in response to light exposure, including c-FOS, Per1 and Per2. These results demonstrate that removing short-wavelengths from polychromatic white light can attenuate circadian phase resetting in an irradiance dependent manner. These results have important implications for designing and optimizing lighting interventions to enhance circadian adaptation.
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http://dx.doi.org/10.3389/fnins.2019.00954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746919PMC
September 2019

A case for the gonadotropin-releasing hormone-agonist trigger in every freeze-all cycle?

Authors:
Robert F Casper

Fertil Steril 2019 08 27;112(2):228-229. Epub 2019 Jun 27.

TRIO Fertility, Division of Reproductive Sciences, University of Toronto, and Lunenfeld-Tanenbaum Research Institute, Mount Sinai Health System, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1016/j.fertnstert.2019.04.041DOI Listing
August 2019

Endometrial compaction (decreased thickness) in response to progesterone results in optimal pregnancy outcome in frozen-thawed embryo transfers.

Fertil Steril 2019 09 24;112(3):503-509.e1. Epub 2019 Jun 24.

TRIO Fertility, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, University of Toronto, and Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada. Electronic address:

Objective: To evaluate whether the change in endometrial thickness between the end of the estrogen phase and the day of embryo transfer has an impact on the pregnancy rate in frozen-thawed embryo transfer (FET) cycles.

Design: Retrospective observational cohort study.

Setting: Single tertiary care medical center.

Patient(s): Ultrasound images in 274 FET cycles were reviewed. All patients underwent endometrial preparation with the use of hormonal therapy.

Interventions(s): Ultrasound measurements of endometrial thickness at the end of the estrogen phase and the day of embryo transfer.

Main Outcome Measure(s): The change in endometrial thickness and ongoing pregnancy rate.

Result(s): We calculated the ongoing pregnancy rate in patients whose endometrial thickness decreased (compacted) after starting progesterone by 5%, 10%, 15%, or 20% compared with patients with no change or increased endometrial thickness. The ongoing pregnancy rate was significantly increased at all levels of compaction compared with no compaction. The ongoing pregnancy rate showed a significant increase with each decreasing quartile of change in thickness (increased percentage of compaction) in the progesterone phase compared with the estrogen phase.

Conclusion(s): There is a highly significant inverse correlation between the ongoing pregnancy rate and the change of endometrial thickness between the end of estrogen administration and the day of embryo transfer.
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http://dx.doi.org/10.1016/j.fertnstert.2019.05.001DOI Listing
September 2019

N° 244 - Endométriose : Diagnostic et prise en charge (résumé/déclarations sommaires et recommandations).

J Obstet Gynaecol Can 2019 Jun;41 Suppl 1:S146-S150

Ottawa (Ont.).

Objectif: Améliorer la compréhension de l'endométriose et fournir une directive clinique factuelle pour ce qui est du diagnostic et de la prise en charge de l'endométriose.

Issues: Parmi les issues évaluées, on trouve les effets de la prise en charge médicale et chirurgicale de l'endométriose sur la morbidité et l'infertilité que connaissent les femmes. MéTHODES: Les membres du comité voué à la présente directive clinique ont été sélectionnés en fonction de leur expertise respective, et ce, en vue de représenter une gamme d'expériences pratiques et universitaires tant au niveau de la représentation géographique au Canada que du type de pratique (nous avons également cherché à nous assurer de représenter l'expertise des sous-spécialités et l'expérience en gynécologie générale). Le comité a analysé toutes les données disponibles issues de la littérature médicale (en anglais et en français), ainsi que les données disponibles issues d'un sondage mené auprès de Canadiennes. Les recommandations ont été formulées sous forme de déclarations de consensus. Le document final a été analysé et approuvé par le comité exécutif et le Conseil de la Société des obstétriciens et gynécologues du Canada. RéSULTATS: Le présent document offre un résumé des derniers résultats en ce qui concerne le diagnostic, les explorations et la prise en charge médicale et chirurgicale de l'endométriose. Les recommandations qui en résultent peuvent être adaptées par chacun des fournisseurs de soins de santé offrant ses services à des femmes qui présentent cette pathologie.

Conclusions: L'endométriose est une pathologie courante et parfois débilitante qui affecte les femmes en âge de procréer. Une approche multidisciplinaire mettant en jeu une combinaison de modifications du mode de vie, de médicaments et de services paramédicaux devrait être utilisée pour limiter les effets de cette pathologie sur les activités de la vie quotidienne et la fertilité. Dans certaines circonstances, le recours à la chirurgie s'avère nécessaire pour confirmer le diagnostic et fournir un traitement cherchant à atteindre l'objectif visé en matière de soulagement de la douleur ou d'amélioration de la fertilité. Les femmes qui obtiennent une stratégie acceptable de prise en charge de cette pathologie peuvent connaître une amélioration de leur qualité de vie ou atteindre leur objectif quant à l'obtention d'une grossesse réussie. DONNéES: Des recherches ont été menées dans les bases de données Medline et Cochrane en vue d'en tirer les articles publiés, en anglais et en français, entre janvier 1999 et octobre 2009 sur les sujets liés à l'endométriose, à la douleur pelvienne et à l'infertilité, et ce, en vue de la rédaction d'une directive clinique de consensus canadienne sur la prise en charge de l'endométriose.

Valeurs: La qualité des résultats a été évaluée au moyen des critères décrits par le Groupe d'étude canadien sur les soins de santé préventifs. Les recommandations quant à la pratique ont été classées en fonction de la méthode décrite par le groupe d'étude. Reportez-vous au Tableau 1. AVANTAGES, DéSAVANTAGES ET COûTS: La mise en œuvre des recommandations de la présente directive clinique entraînera l'amélioration des soins offerts aux femmes dont les douleurs et l'infertilité sont associées à l'endométriose.
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http://dx.doi.org/10.1016/j.jogc.2019.02.133DOI Listing
June 2019

Co-Enzyme Q10 Supplementation Rescues Cumulus Cells Dysfunction in a Maternal Aging Model.

Antioxidants (Basel) 2019 Mar 8;8(3). Epub 2019 Mar 8.

Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, 25 Orde Street, Toronto, ON M5T 3H7, Canada.

Over the past four decades, due to cultural and social changes, women in the developed world have significantly delayed childbirth. This trend is even worse for patients who attend infertility clinics. It is well-known that live birth rates in women older than 35 are significantly lower than in those younger, both naturally and with assisted reproduction. Fertility decline is, in part, due to an increase in oocyte aneuploidy that leads to a reduced embryo quality, as well as an increased incidence of miscarriages and birth defects. Here we show that aging-associated malfunction is not restricted to the oocyte, as cumulus granulosa cells also display a series of defects linked to mitochondrial activity. In, both, human and mouse model, a decline in cumulus cell function due to increased maternal age is accompanied by a decreased expression of enzymes responsible for Coenzyme Q (CoQ) production, particularly Pdss2 and CoQ6. In an aged mouse model supplementation with Coenzyme Q10-a potent stimulator of mitochondrial function-restored cumulus cell number, stimulated glucose uptake, and increased progesterone production. CoQ10 supplementation might, thus, improve oocyte and cumulus cells quantity and quality, by improving the mitochondrial metabolism in females of advanced maternal age.
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http://dx.doi.org/10.3390/antiox8030058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466589PMC
March 2019

What is the optimal timing of embryo transfer when there are only one or two embryos at cleavage stage?

Gynecol Endocrinol 2019 Aug 26;35(8):665-668. Epub 2019 Feb 26.

a TRIO Fertility Partners, Division of Reproductive Sciences , University of Toronto , Toronto , Canada.

Today, most IVF programs have moved to blastocyst transfer but there is still uncertainty regarding when to transfer if there are only one or two embryos at the cleavage stage. The aim of this study was to compare the pregnancy rate of day 3 transfers vs. blastocyst stage transfers in patients who had only one or two embryos on day 3. We conducted a retrospective study of 102 patients with one or two cleavage stage embryos that had their embryos transferred on day 3 and 429 patients had their embryos cultured to day 5 for transfer. The number of mature oocytes (4.0 vs 4.6,  = NS) and number of cleavage stage embryos on day 3 was similar in the two groups (1.3 vs. 1.5,  NS). The clinical pregnancy rate per retrieval (22% vs. 24.6%,  NS) and the ongoing pregnancy rate per retrieval (20% vs. 20.2%,  NS) was comparable between the groups. Fifty seven (13.2%) of the patients had cleavage embryo arrest and did not have an embryo to transfer on day 5. We conclude that the cumulative pregnancy rate is the same for patients with 1-2 cleavage stage embryos regardless of whether the embryo is transferred on day 3 or day 5.
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http://dx.doi.org/10.1080/09513590.2019.1580259DOI Listing
August 2019

Regulating ART: time for a re-think in the light of increasing efficacy, safety and efficiency.

Reprod Biomed Online 2019 04 19;38(4):483-486. Epub 2019 Jan 19.

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK.

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http://dx.doi.org/10.1016/j.rbmo.2019.01.002DOI Listing
April 2019

Developmental potential of slow-developing embryos: day-5 morulae compared with day-5 cavitating morulae.

Fertil Steril 2019 01 12;111(1):105-111. Epub 2018 Nov 12.

TRIO Fertility Partners, Division of Reproductive Sciences, University of Toronto, Toronto, Ontario, Canada.

Objective: To describe and compare the ongoing pregnancy rate between morulae and cavitating morulae (CAVM) transferred on day 5, to describe and compare the blastulation rate between day 5 morulae and CAVM, and to describe the pregnancy rate of these slow-developing blastocysts during a frozen embryo transfer (FET) cycle.

Design: Retrospective cohort study.

Setting: Single tertiary care medical center.

Patient(s): Delayed-development embryos: 3,321 cycles that included 10,304 embryos on day 5 that were cultured until day 6.

Intervention(s): Development of morula and CAVM to the blastocyst stage.

Main Outcome Measure(s): Blastulation rate.

Result(s): The fresh embryo transfers comprised 186 patients with 82 embryos at the morula stage and 104 embryos at the CAVM stage. The pregnancy rate (15.8% vs. 21.1%) and the ongoing pregnancy rate (15.8% vs. 17.3%) were comparable between the groups. The study group included 10,304 day-5 delayed embryos: 5,395 morulae and 4,909 CAVM on day 5. The blastulation rate was statistically significantly higher in the CAVM group compared with the morula group (39.2% vs. 20.4%). We included 201 FET cycles: 77 warmed blastocysts that developed from a morula on day 5 and 124 warmed blastocysts that developed from CAVM on day 5. The clinical pregnancy rate was comparable between the two groups per embryo transfer (21.3% vs. 24.7%).

Conclusion(s): Transferring of fresh, slow-developing embryos seems to improve the cycle outcomes compared with culturing for another day and then vitrifying and thawing later.
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http://dx.doi.org/10.1016/j.fertnstert.2018.08.053DOI Listing
January 2019

Sub-endometrial contractility or computer-enhanced 3-D modeling scoring of the endometrium before embryo transfer: are they better than measuring endometrial thickness?

J Assist Reprod Genet 2019 Jan 25;36(1):139-143. Epub 2018 Oct 25.

TRIO fertility partners, 655 Bay St, Toronto, ON, M5G 2K4, Canada.

Purpose: Recent studies have focused on transvaginal ultrasound measurement (TVUS) of sub-endometrial contractility and computer-enhanced 3-D modeling scoring of the endometrium prior to embryo transfer (ET).The aim of this study was to compare pregnancy outcome of patients who performed the 3-D scoring or the sub-endometrial measurement prior to the ET with patients that did not perform those procedures.

Methods: A single center retrospective cohort study of 635 freeze/thaw cycles of blastocysts vitrified on day 5 and transferred between January 2016 and August 2016.

Results: We compared the patients who performed 3-D scoring with the control group and found comparable patients' characteristics, clinical pregnancy rates (42% vs. 44.3, p = NS, respectively), and ongoing pregnancy rates (31.7% vs. 33.9%, p = NS).We then compared the patients who performed the sub-endometrial wave measurements with the control group and found similar findings. The clinical pregnancy rate (38.2% vs. 44.3, p = NS, respectively) and the ongoing pregnancy rate (30.8% vs. 33.9%) were comparable between the two groups. We performed a regression analysis to examine the independent contribution of different variables to the ongoing pregnancy rates. Both the 3-D and the wave count procedures were not found to have any influence on the ongoing pregnancy rates.

Conclusions: Although new ultrasonic methods of evaluating the endometrium have been proposed during the last years, these methods have not been shown to improve the pregnancy rates compared to the original method of assessing the endometrium by measuring the endometrial thickness.
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http://dx.doi.org/10.1007/s10815-018-1328-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338594PMC
January 2019

Prolonged culture of blastocysts after thawing as a tool for improving prediction of success.

J Assist Reprod Genet 2018 Dec 19;35(12):2195-2199. Epub 2018 Sep 19.

TRIO Fertility Partners, Division of Reproductive Sciences, University of Toronto, 655 Bay St 11th floor, Toronto, ON, M5G 2K4, Canada.

Purpose: A few years ago, we started to use a new freeze-thaw protocol for the frozen embryo transfer cycles. Instead of thawing the embryos 2-4 h prior to the transfer, we started thawing the embryos 20-22 h prior to the transfer. The aim of this study was to compare the pregnancy rate in cases of embryos that continued to develop in the post-thawing culture to that of embryos that did not.

Methods: A retrospective cohort study of blastocyst freeze/thaw cycles vitrified on day 5, thawed and transferred after 20-22 h in the culture, between January 2012 and December 2016.

Results: A total of 375 patients were included in the analysis. Two hundred twenty-eight embryos graded as good, 87 graded as fair, and 60 graded as poor embryos were transferred. The clinical pregnancy rate (50% vs. 19.5% vs 3.3% p < 0.01) and the ongoing pregnancy rate (38.5% vs. 13.6% vs 1.7% p < 0.01) were higher in cases of good embryo quality compared with fair and poor-quality embryos, respectively. For good embryos, progressing to a better grade during the culture did not change the clinical pregnancy rate (51.3% vs. 46.2% p = NS) or the ongoing pregnancy rate (38.5% vs. 37.5% p = NS). For fair embryos, progressing to a better grade during the culture resulted in a higher clinical pregnancy rate (25.4% vs 9% p = 0.05).

Conclusions: The development of the fair embryos in the culture has a highly positive impact on the pregnancy rate and this factor should be taken into consideration before deciding how many embryos to transfer.
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http://dx.doi.org/10.1007/s10815-018-1308-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289927PMC
December 2018

Forty years of IVF.

Fertil Steril 2018 07;110(2):185-324.e5

Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, OH; Department of Obstetrics and Gynecology, University of Alabama at Birmingham School of Medicine, Birmingham, AL; Former Scientific Director/Chief Scientific Officer (2004-2016), American Society for Reproductive Medicine, Birmingham, AL.

This monograph, written by the pioneers of IVF and reproductive medicine, celebrates the history, achievements, and medical advancements made over the last 40 years in this rapidly growing field.
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http://dx.doi.org/10.1016/j.fertnstert.2018.06.005DOI Listing
July 2018

The VEGF and PEDF levels in the follicular fluid of patients co- treated with LETROZOLE and gonadotropins during the stimulation cycle.

Reprod Biol Endocrinol 2018 May 29;16(1):54. Epub 2018 May 29.

Division of Reproductive Sciences, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada.

Background: Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation. The aim of this study was to compare the VEGF and PEDF levels in the follicular fluids of normal responders treated with letrozole and gonadotropins during the ovarian stimulation with patients treated with gonadotropins only.

Methods: A single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits.

Results: The age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209 nmol/l vs. 3280 nmol/l, p = 0.02) were significantly decreased, and the testosterone levels (246.5 nmol/l vs. 40.7 nmol/l, p < 0.001) were significantly increased in the letrozole group compared to the gonadotropin only group. The progesterone levels (21.4 μmol/l vs. 17.5 p = NS) were comparable between the two groups. The VEGF levels (2992 pg/ml vs. 1812 pg/ml p = 0.02) were significantly increased and the PEDF levels (9.7 ng/ml vs 17.3 ng/ml p < 0.001) were significantly decreased in the letrozole group.

Conclusions: Opposite to observations in the mouse, we found that VEGF levels were increased and PEDF levels were decreased in the follicular fluid in patients treated with letrozole during the stimulation cycles. Further investigation is required to determine if patients treated with letrozole during the IVF stimulation protocol are at increased risk for developing OHSS as a result of these findings.
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http://dx.doi.org/10.1186/s12958-018-0367-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975523PMC
May 2018

Does the endometrial receptivity array really provide personalized embryo transfer?

J Assist Reprod Genet 2018 Jul 8;35(7):1301-1305. Epub 2018 May 8.

TRIO Fertility partners, 655 Bay St 11th floor, Toronto, Ontario, M5G 2K4, Canada.

Purpose: The aim of the present study was to determine the percentage of infertility patients who are diagnosed with a non-receptive endometrium according to the endometrial receptivity array (ERA) test and to examine whether adjusting the embryo transfer day according to the proposed shift in the window of implantation improves the pregnancy rate compared to non-ERA-tested patients.

Methods: A single-center retrospective cohort study, including 53 consecutive good prognosis patients (0-2 previous frozen embryo transfers) admitted to our IVF unit for a mock cycle prior to their frozen day-5 embryo (blastocyst) transfer cycle. The mock cycle included an endometrial biopsy for both the ERA test and histological assessment by the Noyes criteria (study group). The next cycle frozen embryo transfer (FET) in the study group was adjusted according to the ERA results. The control group consisted of patients who underwent FET cycles at our clinic during the same period, without performing the endometrial biopsy and ERA testing.

Results: During the study period, 503 patients (control group) underwent FET cycles without performing the ERA testing and 41 patients had FET following an ERA test. There were no between-group differences in patients' age, number of previous transfers, endometrial thickness, number of transferred embryos, and ongoing pregnancy rates (35.2 vs. 39%, respectively, p = NS). Out of the 53 patients who performed the ERA test before their first or second FET, five endometrial samples (9.4%) were found to be post-receptive, 29 (54.7%) pre-receptive, and only 19 samples (35.8%) were receptive. Women in the study group with pre- or post-receptive endometrium on ERA testing, the appropriate adjustment in timing of FET according to the ERA test resulted in a 33.3% pregnancy rate, which is comparable to the 35.2% background ongoing pregnancy rate of the control group.

Conclusions: Performing the ERA test in a mock cycle prior to a FET does not seem to improve the ongoing pregnancy rate in good prognosis patients. Further large prospective studies are needed to elucidate the role of ERA testing in both good prognosis patients and in patients with recurrent implantation failure.
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http://dx.doi.org/10.1007/s10815-018-1190-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063827PMC
July 2018

Off-label Substitutes for Clomiphene Citrate: Author Response.

J Obstet Gynaecol Can 2018 04;40(4):400

McGill University, Montréal, QC.

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http://dx.doi.org/10.1016/j.jogc.2017.10.030DOI Listing
April 2018

Author Response: Delayed Cord Clamping and Umbilical Cord Blood Collection.

J Obstet Gynaecol Can 2018 02;40(2):155

Division of Reproductive Sciences, Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON.

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http://dx.doi.org/10.1016/j.jogc.2017.10.003DOI Listing
February 2018

Oral contraceptive pills as an option for non-surgical management of retained products of conception - a preliminary study.

Gynecol Endocrinol 2018 Jul 18;34(7):609-611. Epub 2018 Jan 18.

a Department of Obstetrics and Gynecology, TRIO Fertility, Toronto and Division of Reproductive Sciences , University of Toronto , Toronto , Canada.

Many Patients with persistent retained products of conception prefers to avoid surgical interventions, such as a dilatation and curettage (D&C) that might pose an additional future risk to their already compromised fertility or obstetric performance. The aim of this study was to the possibility of induced withdrawal bleeding following oral contraceptive administration as a non-surgical treatment for patients with persistent retained products of conception (RPOC). A retrospective study of patients presenting with retained products of conception (RPOC) after failed expectant management or after treatment with PGE1 was performed. Twelve women presenting with RPOC at ≤8 weeks gestation with minimal to mild vaginal bleeding and no signs of infection were treated with oral contraceptive pill (OCP) containing 0.03 mg ethinylestradiol and 0.15 mg of desogestrel for 3 weeks. Out of the 12 patients treated, nine women (75%) successfully expelled the RPOC after completing the three-week course of OCPs. The three cases (25%) that did not resolve following OCP treatment had pregnancy products with positive blood flow on Doppler examination. We conclude that OCPs may be a useful medical treatment option for persisting RPOC in selected patients with absence blood flow on Doppler examination wishing to avoid surgical intervention.
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http://dx.doi.org/10.1080/09513590.2018.1427714DOI Listing
July 2018

Recent advances in fertilization.

F1000Res 2017 31;6:1616. Epub 2017 Aug 31.

Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Toronto and TRIO Fertility, Toronto, Ontario, Canada.

The field of assisted reproductive technology is rapidly progressing with many new advances in the last decade. The present review discusses methods to improve oocyte quality in older women and new stimulation protocols that may improve the number of mature oocytes retrieved during an fertilization cycle. We will discuss the present use of pre-implantation genetic screening (PGS) and finally focus on some new methods to determine endometrial receptivity. The focus of this review is to point out areas of technology that may be controversial or are new enough to require proper controlled studies for validation.
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http://dx.doi.org/10.12688/f1000research.11701.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583738PMC
August 2017

In vitro fertilization treatments with the use of clomiphene citrate or letrozole.

Fertil Steril 2017 10;108(4):568-571

Division of Reproductive Sciences, University of Toronto; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital; and TRIO Fertility, Toronto, Ontario, Canada. Electronic address:

There has been increasing interest in combining the oral agents clomiphene citrate (CC) and letrozole with gonadotropins in IVF: for poor responders to reduce the amount of gonadotropins used, and in normal responders to reduce the incidence of ovarian hyperstimulation (OHSS). In normal responders, mild stimulation with the use of CC and gonadotropins was found to decrease the number of oocytes retrieved and result in good pregnancy rates, but in most studies the cumulative pregnancy rate was lower compared with conventional ovarian stimulation when frozen embryo transfers were considered. Coadministration of letrozole and gonadotropins has mainly been used in patients with breast cancer to prevent the massive elevation of serum E concentrations with the use of standard controlled ovarian hyperstimulation. CC and letrozole have both been used with gonadotropins in poor responders and have been shown to reduce the amount of gonadotropin used without reducing the pregnancy rate. Letrozole use with gonadotropins in IVF cycles may increase endometrial receptivity by increasing integrin expression in the endometrium and by lowering estrogen concentrations to more physiologic levels.
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http://dx.doi.org/10.1016/j.fertnstert.2017.08.017DOI Listing
October 2017

The Refractory Endometrium is Still Refractory.

J Obstet Gynaecol Can 2017 Dec 1;39(12):1188-1191. Epub 2017 Sep 1.

Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada; Toronto Centre for Advanced Reproductive Technology, Toronto, ON, Canada.

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http://dx.doi.org/10.1016/j.jogc.2017.07.006DOI Listing
December 2017

Quand le clomiphène ne sera plus offert….

J Obstet Gynaecol Can 2017 Sep;39(9):715-716

Directeur médical, Toronto Centre for Advanced Reproductive Technology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario.

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http://dx.doi.org/10.1016/j.jogc.2017.06.024DOI Listing
September 2017