Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women

doi:10.1016/j.fertnstert.2012.05.042

Fertility and Sterility

Volume 98, Issue 3, September 2012, Pages 657-663

https://doi.org/10.1016/j.fertnstert.2012.05.042 Get rights and content

Objective

To estimate the probability of live birth, adverse treatment outcome, and extremes of ovarian response at different antral follicle count (AFC) cutoff levels in a large prospective cohort of women undergoing IVF treatment.

Design

Prospective study.

Setting

University-based assisted conception unit.

Patient(s)

A total of 1,012 consecutive subjects of all ages undergoing their first cycle of assisted reproductive techniques.

Intervention(s)

Transvaginal three-dimensional ultrasound assessment and venipuncture in the early follicular phase of the menstrual cycle.

Main Outcome Measure(s)

Live birth rate, poor ovarian response, and ovarian hyperstimulation syndrome (OHSS).

Result(s)

Analysis was performed in 1,012 subjects. Both age (r = 0.88) and AFC (r = 0.92) thresholds show significant linear relationship with the probability of live birth, but AFC demonstrates a stronger correlation. At AFC quartiles of 3–10, 11–15, 16–22, and ≥23, the mean live birth rates were 23%, 34%, 39%, and 44%, respectively. No live birth was observed in women with AFC <4. Antral follicle count was predictive of ovarian response, with a 67% likelihood of poor ovarian response for AFC ≤4. Although the risk of moderate or severe OHSS is 2.2% with AFC of ≤24, the risk increases to 8.6% at AFC of ≥24. The risk of OHSS increases further to 11% if there are signs and symptoms of polycystic ovary syndrome.

Conclusion(s)

Although age and AFC are significantly correlated with live birth, AFC demonstrates a stronger correlation. Antral follicle count thresholds are useful to predict live birth rates and risks of poor ovarian response and OHSS during IVF treatment.

Section snippets

Experimental Design

In this prospective, observational study we aimed to recruit all subjects who were undergoing their first cycle of IVF or intracytoplasmic sperm injection (ICSI) treatment. The study was performed at the University of Nottingham's Assisted Conception Unit (Nurture Fertility: Nottingham University Research and Treatment Unit in Reproduction) and included all subjects who met the above criterion between March 2005 and July 2009. Subjects were excluded if they were found to have an ovarian cyst or

Results

A total of 1,120 subjects were recruited. Of these, 27 were excluded owing to the presence of an ovarian cyst(s), leaving 1,093 subjects. Of the 1,030 subjects who subsequently began treatment, 18 failed to down-regulate, leaving 1,012 for the final analysis. The mean ± SD (range) age, body mass index (BMI), basal FSH, AFC, and ovarian volume were 34.3 ± 4.3 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 years, 24.4 ± 3.5 18, 19, 20, 21, 22, 23, 24, 25

Discussion

This is the first study using a large population to report the probabilities of live birth and the risks of adverse treatment outcome that can occur during ART, based on different thresholds of AFC measured using 3D ultrasound. The data confirm that AFC is a significant predictor of live birth, poor ovarian response, and moderate or severe OHSS. Although AFC offers the best predictive ability for determining poor ovarian response and OHSS among all the conventional ovarian reserve markers

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Heterogeneous by nature, polycystic ovary syndrome (PCOS) consists of a combination of signs and symptoms of androgen excess and ovarian dysfunction in the absence of other specific diagnoses. In addition, PCOS is frequently associated with abdominal adiposity, insulin resistance, obesity, metabolic disorders, and cardiovascular risk factors. Mounting evidence suggests that PCOS is a complex multigenic disorder with strong epigenetic and environmental influences, including diet and lifestyle factors that vary widely among individual patients. This chapter will address the challenge imposed historically by the intrinsic heterogeneity of PCOS on the criteria used for its definition, proposing strategies directed to overcome the limitations derived from such variability on our understanding of the disorder.
A comparison of two- and three-dimensional ultrasonographic methods for evaluation of ovarian follicle counts and classification of polycystic ovarian morphology
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To determine the level of agreement across assessments of follicle number per ovary (FNPO) and classifying of polycystic ovarian morphology (PCOM; FNPO ≥25) with the use of various real-time (RT) and off-line two-dimensional (2D) and three-dimensional (3D) ultrasonographic methods.
Method comparison study.
University-based clinical research unit.
Sixteen women with and without PCOM.
Thirty-two ovaries were analyzed with the use of eight ultrasonographic methods: 2D-Grid (reference method), 2D-RT, 2D-RT with Grid, multiplanar view (MPV), MPV-RT, tomographic ultrasound imaging (TUI), TUI-RT, and semiautomated volume calculation (SonoAVC).
FNPO, PCOM status, and time to obtain FNPO. Clinical feasibility, defined as the time taken to obtain FNPO, also was evaluated.
2D-RT overestimated FNPO versus 2D-Grid (3 ± 9 follicles) owing to overcounting in non-PCOM ovaries (6 ± 6 follicles). However, systematic bias was not detected when a grid overlay was incorporated (2D-RT with Grid). SonoAVC underestimated FNPO (−3 ± 5 follicles), particularly in PCOM ovaries (−4.1 ± 5.0 follicles). No bias in FNPO was detected between MPV, TUI, or TUI-RT versus 2D-Grid. 2D-RT significantly misclassified ovaries as PCOM. All methods except MPV took less time to complete FNPO assessments compared with 2D-Grid.
Variability in FNPO across ultrasonographic methods limits their interchangeable use, particularly when a precise metric is needed. 2D-RT may be problematic owing to its propensity to misclassify PCOM. 2D-RT with Grid and MPV-RT could represent clinically feasible alternatives to obtain FNPO and classify PCOM. Efforts to reduce variation in FNPO will clarify the relevance of PCOM in women’s health.
Una comparación de métodos ecográficos bidimensionales y tridimensionales para la evaluación del recuento de folículos ováricos y la clasificación de la morfología del ovario poliquístico.
Determinar el nivel de concordancia entre las evaluaciones del número de folículos por ovario (FNPO) y la clasificación de la morfología de ovario poliquístico (PCOM; FNPO ≥25) con el uso de varios métodos bidimensionales en tiempo real (RT) y off-line ( Métodos ecográficos 2D) y tridimensionales (3D).
Estudio comparativo de métodos.
Institución académica.
Dieciséis mujeres con y sin PCOM.
Se analizaron treinta y dos ovarios con el uso de ocho métodos ecográficos: 2D-Grid (método de referencia), 2D-RT, 2D-RT con Grid, vista multiplanar (MPV), MPV-RT, ecografía tomográfica (TUI) , TUI-RT y cálculo de volumen semiautomático (SonoAVC).
FNPO, estado de PCOM y tiempo para obtener FNPO. También se evaluó la factibilidad clínica, definida como el tiempo necesario para obtener FNPO.
2D-RT sobreestimó FNPO versus 2D-Grid (3 ± 9 folículos) debido al recuento excesivo en ovarios sin PCOM (6 ± 6 folículos). Sin embargo, no se detectó un sesgo sistemático cuando se incorporó una superposición de cuadrícula (2D-RT con cuadrícula). SonoAVC subestimó la FNPO (−3 ± 5 folículos), particularmente en los ovarios PCOM (−4,1 ± 5,0 folículos). No se detectó sesgo en FNPO entre MPV, TUI o TUI-RT versus 2D-Grid. 2D-RT clasificó erróneamente los ovarios como PCOM. Todos los métodos, excepto MPV, tomaron menos tiempo para completar las evaluaciones de FNPO en comparación con 2D-Grid.
La variabilidad en la FNPO entre los métodos ecográficos limita su uso intercambiable, particularmente cuando se necesita una métrica precisa. 2D-RT puede ser problemático debido a su propensión a clasificar erróneamente PCOM. 2D-RT con Grid y MPV-RT podrían representar alternativas clínicamente factibles para obtener FNPO y clasificar PCOM. Los esfuerzos para reducir la variación en FNPO aclararán la relevancia de PCOM en la salud de la mujer.
Effect of GnRH-antagonist, mifepristone and letrozole on preventing ovarian hyperstimulation syndrome in rat model
2021, Reproductive BioMedicine Online
Can luteolysis-targeted drugs, gonadotrophin-releasing hormone antagonist (GnRH-ant), mifepristone and letrozole, administered separately or in combination, prevent the progression of ovarian hyperstimulation syndrome (OHSS) in a rat model?
Thirty-six female Wistar rats were randomly divided into six groups, including control group (OHSS group, ovarian hyperstimulation-induced OHSS); GnRH-ant group (OHSS with GnRH-ant treatment); mifepristone group (OHSS with mifepristone treatment); letrozole group (OHSS with letrozole treatment); combination group (OHSS with GnRH-ant, mifepristone and letrozole treatment in combination). The main outcomes were the alterations in OHSS-related indices, including ovarian weight, vascular permeability, serum oestradiol and progesterone levels, corpus luteum proportion and diameter, ovarian vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), caspase-3 and cleaved caspase-3 levels.
No significant difference was found in body weight gain among the six groups. Compared with the control group, the OHSS group showed significant increases in all OHSS-related indices. GnRH-ant treatment showed decreases in vascular permeability, serum oestradiol level, corpus luteum diameter, ovarian VEGF /IL-6 mRNA levels, and increases in ovarian caspase-3 and cleaved caspase-3 levels. Mifepristone treatment demonstrated reduction in serum progesterone level and corpus luteum diameter, and elevation in ovarian caspase-3 and cleaved caspase-3 levels. Letrozole treatment displayed a decline in serum oestradiol level and corpus luteum diameter, and up-regulation in ovarian caspase-3 and cleaved caspase-3 levels. The combination treatment by GnRH-ant, mifepristone and letrozole showed enhanced synergistic effect on reducing OHSS-related indices.
GnRH-ant, mifepristone and letrozole are beneficial in preventing the progression of OHSS through different luteolytic mechanisms. Cocktail style treatment shows enhanced synergistic effect on preventing the progression of OHSS.
Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals
2021, Reproductive BioMedicine Online
Citation Excerpt :
In addition, this is the first study to analyse the risk factors for hemoperitoneum. The incidences of moderate-to-severe OHSS and severe hemoperitoneum were 1–5% (Jayaprakasan et al., 2012; Kahnberg et al., 2009; Luke et al., 2010; Papanikolaou et al., 2006; Practice Committee of the American Society for Reproductive Medicine, 2016; Steward et al., 2014) and 0.04–0.23%, respectively (Aragona et al., 2011; Bennett et al., 1993; Dicker et al., 1993; Govaerts et al., 1998; Levi-Setti et al., 2018; Liberty et al., 2010; Nouri et al., 2014; Zhen et al., 2010), according to other reports of complications in ART treatment. In Japan, the incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08% of ART cycles, respectively, which is either comparable to or less than the incidence in other countries.
What are the risk factors affecting the incidences of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and severe hemoperitoneum in assisted reproductive technology (ART) treatment cycles?
A retrospective cohort study was conducted on 1,435,108 oocyte retrieval cycles among Japanese ART registry data between 2007 and 2015. The study included 11,378 cycles with moderate-to-severe OHSS, 1182 cycles with severe hemoperitoneum, including 27 cycles with both conditions, and 1,422,575 cycles without moderate-to-severe OHSS and severe hemoperitoneum.
The incidences of moderate-to-severe OHSS and severe hemoperitoneum were 0.79% and 0.08%, respectively, and decreased by 0.57-fold and 0.29-fold from 2007 to 2015, respectively. In cycles with OHSS and cycles with hemoperitoneum women were younger (odds ratios [OR] 0.91 and 0.95, respectively) and had more retrieved oocytes (OR 1.09 and 1.01, respectively) compared with cycles without both complications. The use of a gonadotrophin-releasing hormone (GnRH) agonist protocol for ovarian stimulation was the highest risk factor in cycles with OHSS and hemoperitoneum (OR 1.83 and 1.24, respectively), followed by GnRH antagonist protocol (reference), gonadotrophin with or without oral medicine (OR 0.45 and 0.56, respectively) and natural or oral medicine (OR 0.02 and 0.19, respectively). In fresh embryo transfer, clinical pregnancy was associated with an increased risk of OHSS and hemoperitoneum (OR 1.19 and 2.34, respectively).
The highest risk factors affecting OHSS and hemoperitoneum were the use of a GnRH agonist protocol and clinical pregnancy following fresh embryo transfer. The incidences of OHSS and hemoperitoneum have decreased yearly with a reduction of GnRH agonist use and fresh embryo transfer.
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: K.J. has nothing to disclose. Y.C. has nothing to disclose. R.I. has nothing to disclose. Z.H. has nothing to disclose. J.H. has nothing to disclose. A.C. has nothing to disclose. N.R.-F. has nothing to disclose.

: This study was funded by the University of Nottingham.

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Original articlePrediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women

Objective

Design

Setting

Patient(s)

Intervention(s)

Main Outcome Measure(s)

Result(s)

Conclusion(s)

Section snippets

Experimental Design

Results

Discussion

Fertil Steril

Lancet

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Obstet Gynecol

Lancet

Fertil Steril

Fertil Steril

Reprod Biomed Online

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Ultrasound Med Biol

Curr Obstet Gynaecol

Reprod Biomed Online

Trends Endocrinol Metab

Reprod Biomed Online

Eur J Obstet Gynecol Reprod Biol

Original article
Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women