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      The impact of a thin endometrial lining on fresh and frozen–thaw IVF outcomes: an analysis of over 40 000 embryo transfers

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          Abstract

          STUDY QUESTION

          Does each millimeter decrease in endometrial thickness lead to lower pregnancy and live birth rates in fresh and frozen IVF cycles?

          SUMMARY ANSWER

          Clinical pregnancy and live birth rates decline as the endometrial thickness decreases below 8 mm in fresh IVF-ET and below 7 mm in frozen–thaw embryo transfer (ET) cycles.

          WHAT IS KNOWN ALREADY

          Previous studies have been heterogenous and have shown conflicting results on the impact of endometrial thickness on IVF outcomes. Most studies do not include many patients with an endometrial thickness below 6 mm, and there are few studies of frozen–thaw ET cycles.

          STUDY DESIGN, SIZE, DURATION

          This study is a retrospective cohort analysis of all Canadian IVF fresh and frozen–thaw ET cycles from the CARTR-BORN database for autologous and donor fresh and frozen–thaw IVF-ET cycles from 1 January 2013 to 31 December 2015. A total of 24 363 fresh and 20 114 frozen–thaw IVF-ET cycles were reported during this timeframe.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          33 Canadians clinics participated in voluntary reporting of IVF and pregnancy outcomes to the CARTR-BORN database. The impact of endometrial thickness on pregnancy, live birth and pregnancy loss rates were analyzed for fresh IVF-ET and frozen–thaw cycles.

          MAIN RESULTS AND THE ROLE OF CHANCE

          In fresh IVF-ET cycles, clinical pregnancy and live birth rates decreased ( P < 0.0001) and pregnancy loss rates increased ( P = 0.01) with each millimeter decline in endometrial thickness below 8 mm. Live birth rates were 33.7, 25.5, 24.6 and 18.1% for endometrial thickness ≥8, 7–7.9, 6–6.9 and 5–5.9 mm, respectively. In frozen–thaw ET cycles, clinical pregnancy ( P = 0.007) and live birth rates decreased ( P = 0.002) with each millimeter decline in endometrial thickness below 7 mm, with no significant difference in pregnancy loss rates. Live birth rates were 28.4, 27.4, 23.7, 15 and 21.2% for endometrial thickness ≥8, 7–7.9, 6–6.9, 5–5.9 and 4–4.9 mm, respectively. The likelihood of achieving an endometrial thickness ≥8 mm decreased with age (89.7, 87.8 and 83.9% in women <35, 35–39 and ≥40, respectively) ( P < 0.0001).

          LIMITATIONS, REASONS FOR CAUTION

          This study only included cycles which proceeded to ET, which may overestimate pregnancy outcomes. Approximately 8% of cycles could not be included in the analysis due to data irregularity related to data entry. Demographic data aside from age were unavailable but may be important as lower endometrial thickness may be associated with poor ovarian response.

          WIDER IMPLICATIONS OF THE FINDINGS

          Although pregnancy and live birth rates decrease with endometrial thickness, reasonable outcomes were obtained even with lower endometrial thickness measurements. These data provide valuable guidance for both physicians and patients when confronted with decisions related to a persistently thin endometrium.

          STUDY FUNDING/COMPETING INTEREST(S)

          This study was not funded. The authors do not have any conflicts of interests to declare.

          TRIAL REGISTRATION NUMBER

          N/A.

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          Most cited references14

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          Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers.

          To construct a prediction model for live birth after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and single-embryo transfer (SET) after 2 days of embryo culture.
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            The relationship between endometrial thickness and outcome of medicated frozen embryo replacement cycles.

            To examine the relationship between endometrial thickness and outcome of medicated frozen-thawed embryo replacement (FER) cycles. A retrospective observational study. Assisted conception unit at a university hospital. All patients who underwent an FER cycle between 1997 and April 2006 and met the inclusion criteria. For endometrial preparation, a daily dose of 6 mg of oral E(2) valerate was started on menstrual day 1, and P pessaries (800 mg daily) were administrated when the endometrial thickness had reached 7 mm or more, with ET taking place 2-3 days later. The FER cycles were categorized according to endometrial thickness measurement on the day of P supplementation. Implantation, clinical pregnancy, ongoing pregnancy, and live birth rates. In all, 768 consecutive medicated FER cycles were analyzed. The lowest pregnancy rates were associated with endometrial thickness 14 mm (n = 12; 7% in both groups). Significantly higher implantation (19% vs. 12%), clinical pregnancy (30% vs. 18%), ongoing pregnancy (27% vs. 16%), and live birth (25% vs. 14%) rates were achieved in cycles where endometrial thickness was 9-14 mm (n = 386), compared with those in which endometrial thickness was 7-8 mm (n = 357). These differences remained significant after adjusting for confounding variables (adjusted odds ratio [OR] = 1.83 [confidence interval {CI} = 1.3-2.6] for clinical pregnancy, 1.8 [CI = 1.2-2.6] for ongoing pregnancy and 1.9 [CI = 1.3-2.8] for live birth). In medicated FER cycles, an endometrial thickness of 9-14 mm measured on the day of P supplementation is associated with higher implantation and pregnancy rates compared with an endometrial thickness of 7-8 mm.
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              The effect of endometrial thickness on IVF/ICSI outcome.

              During the menstrual cycle the endometrium undergoes cyclic proliferative and secretory changes in preparation for implantation. If this preparation is not sufficient, then implantation will fail. The impact of endometrial thickness on the day of embryo transfer on IVF outcome was investigated in the present study. A retrospective analysis was conducted of 1228 IVF/ICSI cycles. Stimulation was with clomiphene citrate (CC) + hMG in one-third of the cycles, and ultrashort GnRH agonist stimulation in two-thirds. Cycle parameters were compared between pregnant and non-pregnant patients. A similar comparison was made between ongoing pregnancies and those that resulted in a loss. There were more follicles, oocytes and embryos, the endometrium was thicker and the embryo quality was higher among women who became pregnant when compared with non-pregnant women after assisted reproduction. The pregnancy rate improved as endometrial thickness increased. No difference in cycle parameters and endometrial thickness was found between ongoing pregnancies and pregnancies that resulted in a first-trimester loss. CC had no measurable adverse endometrial effect, but the pregnancy rate was lower in CC+hMG cycles. Increased endometrial thickness is associated with higher pregnancy rates. However, neither attainment of pregnancy nor pregnancy outcome was predicted by endometrial thickness alone.
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                Author and article information

                Journal
                Hum Reprod
                Hum. Reprod
                humrep
                Human Reproduction (Oxford, England)
                Oxford University Press
                0268-1161
                1460-2350
                October 2018
                17 September 2018
                17 September 2018
                : 33
                : 10
                : 1883-1888
                Affiliations
                [1 ]Mount Sinai Fertility, 250 Dundas St. W, Suite 700, Toronto, Ontario, Canada
                [2 ]Department of Obstetrics and Gynecology, Mount Sinai Hospital, 600 University Ave., University of Toronto, Toronto, Ontario, Canada
                [3 ]Trio Fertility, 655 Bay St., Suite 1101, Toronto, Ontario, Canada
                [4 ]True North Imaging, 7330 Yonge St., Thornhill, Ontario, Canada
                [5 ]Lunenfeld-Tanenbaum Research Institute, Prosserman Population Health Center, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, Canada
                [6 ]The Montreal Fertility Centre, 5252 Boulevard de Maisonneuve O, #220, Montreal, Québec, Canada
                Author notes
                Correspondence address. Mount Sinai Fertility, 250 Dundas St W., Suite 700, Toronto, Ontario, Canada M5T 2Z5. E-mail: Kimberly.liu@ 123456sinaihealthsystem.ca
                Author information
                http://orcid.org/0000-0002-8640-4414
                Article
                dey281
                10.1093/humrep/dey281
                6145412
                30239738
                0a05296c-7fa8-44bb-a22f-b8460e90b3e4
                © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 11 June 2018
                : 11 August 2018
                : 24 August 2018
                Page count
                Pages: 8
                Categories
                Original Article
                Infertility

                Human biology
                art,ivf,endometrial thickness,pregnancy outcomes,live birth
                Human biology
                art, ivf, endometrial thickness, pregnancy outcomes, live birth

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