Optimizing Ovulation Induction in the Poor Responder
Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: IVF Poor Responders
Intervention: Estradiol (Drug); Oral Contraceptive Pills (OCP) (Drug)
Phase: N/A
Status: Withdrawn
Sponsored by: Duke University Official(s) and/or principal investigator(s): Susannah D Copland, MD, Principal Investigator, Affiliation: Duke University Donna Sessions, MD, Principal Investigator, Affiliation: Emory University
Summary
The purpose of this randomized controlled trial is to compare the efficacy and effect of
luteal estradiol and combined oral contraceptive pills (COPC) on follicle recruitment and
synchrony in a poor responder population. The randomized groups consist of: 1. patients
receiving luteal estradiol prior to ovulation induction; and 2. patients receiving COCPs for
1 month prior to ovulation induction. Follicle characteristics and serum biomarkers will be
followed and compared in each group. Coefficient of variation will be used to evaluate
follicle size discrepancy. Chi square analysis will be used to compare categorical variables
between treatment groups. Both estradiol and COPCs are used clinically in assisted
reproduction, so this study affords no additional risks to the participants.
Clinical Details
Official title: Optimizing Ovulation Induction in the Poor Responder: a Randomized Clinical Trial of Luteal Phase Estradiol Versus Combined Oral Contraceptive Pill on Ovarian Morphology and Biomarkers Prior to Ovulation Induction
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Follicular response and synchrony
Secondary outcome: IVF outcomes
Detailed description:
1. Protocol Title:
Optimizing ovulation induction in the poor responder: a randomized controlled trial of
luteal phase estradiol verses combined oral contraceptive pill (COCP) on ovarian
morphology and biomarkers prior to ovulation induction
2. Purpose of the Study:
In women undergoing ovulation induction who are at high risk for poor response, we
hypothesize that:
Null Hypothesis: Mean follicular diameter and coefficient of variation between
follicles in patients receiving luteal COCP are statistically equal to follicular
diameters and coefficient of variation between follicles in patients receiving
estradiol. To test this hypothesis, the specific aims of the present proposal are:
Aim 1: Compare the effect of luteal estradiol and COCP pretreatment on follicle
synchrony. Mean follicular diameter and the coefficient of variation between follicle
measurements will be calculated on cycle day 3 the cycle before and during treatment.
Aim 2: Compare the effect of luteal estradiol and COCP pretreatment on follicle
recruitment. Markers of follicle recruitment will be measured on cycle day 3 before and
during the treatment cycle. Previously identified follicle recruitment markers that
positively correlate with follicle recruitment include: antral follicle count (AFC),
AMH and androstenedione.
Aim 3: Compare the efficacy of luteal estradiol and COCP. The number of mature
follicles greater than or equal to 14 mm on day of hCG and pregnancy outcomes will be
recorded.
The two treatment groups are:
- Group 1: Luteal estradiol administration prior to ovulation induction management
per patient's primary physician.
- Group 2: COCP administration for one month prior to ovulation induction management
per patient's primary physician.
Upon completion, we will have compared follicular and biochemical ovarian response to
luteal estradiol and COCPs in poor responders undergoing ovulation induction. The
future implications of this study are development of clinical strategies for treating
patients at high risk of poor response.
3. Background & Significance:
Ten percent of the United States population, 6. 2 million women and their partners,
reported infertility in the 1995 National Survey of Family Growth. The number of
couples affected by infertility is predicted to increase to 6. 5 million by the year
2025.' Among women seeking infertility treatment, a subset will be classified as poor
responders due to poor ovarian response to treatment. Though the definition of poor
response to treatment is not standardized, studies estimate that 4-26% of patients
undergoing treatment are affected. 2 The proportion of women classified as poor
responders may increase as more women delay fertility until an age of decreased
fecundity due to declining ovarian reserve. Establishing effective treatments for poor
responders is therefore imperative.
The principal goal of ovulation induction in infertile patients with regular menstrual
cycles is to achieve two to three mature synchronous follicles to maximize chance of
pregnancy and minimize risk of ovarian hyperstimulation syndrome. Poor responders, by
definition, have a lower likelihood of sufficient follicular recruitment. Lesser
recruitment can be compounded by follicular dysynchrony that necessitates human
chorionic gonadotropin (hCG) administration based on larger follicles when lagging
smaller follicles are less likely to be mature. Follicular dysynchrony can be
compounded by the rise in follicle stimulating hormone (FSH) in the luteal phase.
Fanchin et al has demonstrated that luteal estradiol administration suppresses luteal
FSH rise, reduces antral follicle size, and synchronizes the follicular cohort. 3,4,5,6
Luteal estradiol and GnRH antagonist administration prior to controlled ovarian
hyperstimulation for in vitro fertilization (IVF) have been shown to decrease
cancellation rate, increase mean number of oocytes retrieved, and improve fertilization
rates in poor responders (retrospective study using historic controls presented in
abstract form).7 Estradiol has also been used in patients with hypergonadotrophic
amenorrhea to suppress elevated endogenous LH and FSH prior to stimulation with
exogenous gonadotropins with modest success in achieving ovulation and, in rare cases,
pregnancy. 8
Combined oral contraceptive pills (COCPs) administered prior to ovulation induction in
IVF increase the number of oocytes retrieved and suppress cyst formation. 9,10,11 In a
small study of poor responders undergoing controlled ovarian hyperstimulation for IVF,
pretreatment with COCPs was associated with increased pregnancy rates compared to
pretreatment with luteal phase gonadotropin releasing hormone agonist (GnRH-a),
follicular phase GnRH-a, and no pretreatment. 12 COCPs prior to ovulation induction with
microdoses of GnRHa and gonadotropins enhance ovarian responsiveness in poor responders
resulting in higher peak estradiol (E2) levels, more mature follicles, and larger
number of retrieved oocytes when compared with traditional luteal GnRH-a downregulation
followed by gonadotropin stimulation. 13 Follicular GnRH-a administration releases
endogenous gonadotropins producing a gonadotropin "flare" effect. Smaller, more
frequent "microdosing" of GnRH-a minimizes endogenous FSH suppression while preventing
premature luteinizing hormone (LH) surges. Oral contraceptive pretreatment prevents
formation of a corpus luteum that could produce progesterone prematurely during the
flare. This protocol with the addition of growth hormone (GH) has been shown to produce
a 50% ongoing pregnancy rate (PR) when used in patients who had prior ovulation
induction cycles using luteal phase GnRH-a suppression followed by exogenous
gonadotropins and GH cancelled due to poor response. 14
While both COCPs and luteal estradiol suppress the luteal rise in FSH and synchronize
follicles, they have not been compared against each other. COCPs, with progestin in
addition to estrogen, may achieve better suppression of luteal FSH than estradiol and
result in better synchronization of the follicles. COCPs, however, have been used to
decrease ovarian responsiveness in patients with polycystic ovarian syndrome who are at
increased risk of ovarian hyperstimulation syndrome. 15 Therefore, COCPs may suppress
ovarian responsiveness more than luteal estradiol, an unwanted effect in the poor
responder population. One potential mechanism for greater ovarian suppression with
COCPs may be the decrease in androstenedione, a marker shown to be positively
correlated with total and mature oocyte number obtained during IVF, 16 subsequent to
the COCP-induced increase in sex hormone binding globulin.
Previously identified follicle recruitment markers include antral follicle count (AFC)
and androstenedione which positively correlate with follicle recruitment. 16 AFC is a
reproducible predictor of follicular recruitment which has been shown to positively
correlate with number of oocytes retrieved and IVF pregnancy outcome. 18,19, 20 AFC
measurements are stable throughout the ovarian cycle and before and after GnRH
downregulation. 21
AMH may serve as a biomarker for both follicle quantity and quality since both serum
and intrafollicular AMH positively correlate with AFC and number of eggs retrieved
during IVF. 22 The mid-luteal AMH rise may reflect luteal follicle development;23 both
estradiol and COCP may affect luteal follicle development therefore CD3 AMH levels
before and after treatment will be of great interest. AMH also exhibits superior cycle
to cycle reproducibility when compared to FSH, E2, inhibin Band AFC. 24
4. Design & Procedures:
The study is a randomized controlled trial.
Pretreatment Evaluation
Baseline studies preceding ovulation induction:
Cycle day 3 FSH, inhibin B, estradiol, androstenedione, AMH, and AFC will be performed the
cycle of OCP or luteal pretreatment and the cycle of ovulation induction.
Transvaginal ultrasound:
• Ovarian morphology and dimensions will be obtained using a vaginal probe ultrasound. All
study ultrasounds will be recorded and read by a single investigator (at each center)
blinded to patient treatment group.
- Ovarian volume will be calculated using the formula for a prolate ellipsoid
(0. 5237xD1xD2xD3; D1, D2, and D3 are the maximal longitudinal anteroposterior and
transverse diameters, respectively).
- Ovarian volume will also be calculated using the VOCAL (volume calculation) GE software
package on the Voluson ultrasound machine.
- Antral follicles will be counted, measured in two dimensions and averaged.
Blood sampling:
- Blood samples will be used to measure FSH, inhibin B, estradiol, androstenedione, AMH,
and progesterone during the cycle prior to and of ovarian stimulation.
- Estradiol, FSH, progesterone, inhibin B, androstenedione, and AMH will be transported
to, stored and measured in batches at Dr. Sarah Berga's Emory University research
laboratory, Duke Fertility Center or the Duke Unievrsity Hospital core laboratory.
Registration/Randomization
Block randomization will occur by computer algorithm to two groups:
- Group 1: Luteal estradiol
- Group 2: COCP
Therapy
1. Ovarian stimulation for ovulation induction:
Group 1: Luteal estradiol • Starting cycle day 20, two 0. 1 mg/d transdermal estradiol
patch will be applied every other day until cycle day 2.
- Patients will present for baseline ultrasound, AFC, FSH, inhibin B, estradiol,
progesterone, androstenedione, and AMH measurement on cycle day 3.
- Starting on cycle day 3, ovarian stimulation will begin. The treatment protocol
for ovulation induction will be determined by the patient's primary physician and
the clinician monitoring the cycle.
Group 2: Combined oral contraceptive
• Patients will begin COCP administration on the cycle day one of the cycle prior to
ovarian stimulation.
• Patients will present for baseline ultrasound, AFC, FSH, inhibin B, estradiol,
progesterone, androstenedione, and AMH measurement on cycle day 3.
• Starting on cycle day 3, ovarian stimulation will begin. The treatment protocol for
ovulation induction will be determined by the patient's primary physician and the
clinician monitoring the cycle.
All participants will be monitored by serum E2 levels and TVUS as determined by the
patient's primary physician to assess the rise in circulating estrogen levels and
follicular maturation. Follicles will be measured in two dimensions and the average
recorded.
2. The mode of ovulation trigger, and IUI or IVF will be at the discretion of the
patient's primary physician and the clinician monitoring the cycle.
Patient Assessment
Patients will return 14 days after IUI or IVF for serum beta hCG testing. In the event
of a negative pregnancy test, patients will be given the option of crossing over to the
other treatment group.
Data Collection
Clinical Information/Clinical Data Items:
• Age
• Infertility diagnoses
• Prior dates and specifics of infertility treatments and results
• Prior cycle characteristics: antral follicle count (AFC) and dimensions, ovarian
volume, FSH, inhibin A, E2, progesterone, androstenedione, and AMH before and during
treatment
• Peak E2
• Outcome: Mean follicular diameter and the coefficient of variation between follicles
on cycle day 3 before and during treatment
• Number of mature follicles greater than or equal to 14 mm on day of hCG
- β-hCG result
5. Selection of Subjects:
The Emory Reproductive Center (ERC) and Duke Fertility Center (DFC) are assisted
reproductive technology centers offering ovulation induction, IVF, gamete micromanipulation,
and embryo cryopreservation. Between the two centers, approximately 250-300 stimulated
cycles are completed each year. While the study is open, all women at risk for poor response
to ovulation induction at the two centers will be offered participation by the PI, Co-PI,
Co-Investigator or coordinating research nurse.
Inclusion Criteria:
- Antral follicle count < 8
- Antimullerian hormone (AMH) <1. 3
- Follicle stimulating hormone (FSH)>10
- History of follicular dysynchrony or poor response
Exclusion Criteria:
• Menopause
- FSH >40
- Age > 50
- Contraindication to estradiol or COCP (including pre-existing cardiovascular disease,
familial thrombophilia (factor V Leiden), severe hypercholesterolemia, smoker over age
35) Ovulation induction during month of estradiol treatment
6. Subject Recruitment & Compensation:
Please see section #5. There will be no patient compensation.
7. Consent Process:
An IRB-approved written informed consent will be obtained from each subject at entry into
the study; elements of informed consent will include: (a) having the subject review the
study consent form; (b) having the investigator(s) or study staff meet with the subject to
review the consent, confirm understanding, and answer any questions; and (c) once the
investigator(s) or study staff are convinced that the protocol is understood and that there
is agreement to participate, having the consent signed in the presence of a witness. The
potential participant will have until the beginning of her first stimulated cycle to decide
whether or not she is participating in the study. The consent will be discussed and signed
in person at Emory Reproductive Center or Duke Fertility Center. The consent process, as
outlined above, will occur in private consultation rooms. There is no time minimum or
maximum for the consent process. The consent process is determined to be complete when the
participant verbalizes understanding, states that she has no further questions and signs the
consent forms. The PI, Co-PI, Co-Investigators and coordinating research nurse will be
readily available by telephone or in person at ERC and/or DFC to answer questions concerning
the consent. In order to reduce potential coercion and perceived influence by the study
personnel, the study details and consent forms will be discussed in a matter-of-fact and
consistent manner. Only patients who speak and read English will be admitted into the study.
8. Subject's Capacity to Give Legally Effective Consent:
Only patients with the capacity to give legally effective consent will be included in the
study.
9. Study Interventions:
Please see section #4.
10. Risk/Benefit Assessment:
The treatments used in this study have been studied individually and are used in clinical
practice. Our goal is to see which one is better. Therefore the risks of this study are the
same as the risk of ovulation induction to which the subjects will be exposed whether they
are enrolled in the study or not.
11. Costs to the Subject:
There is no additional cost to the subject above the regular fees assessed for ART.
12. Data Analysis & Statistical Considerations:
Coefficient of variation will be used to evaluate follicular size discrepancy by the
following formula: Coefficient of variation = 100 * Standard deviation / mean of the set
Sample Size
We predict that a difference of 1. 2 mm between mean follicular size before and after COCPs
will be clinically significant. This is based on observations by Fanchin in which women
treated with luteal estradiol displayed a decrease in mean follicular size on day 3 of 1. 2
mm that was associated with a significant decrease in coefficient of variation between
follicles and an increase in mature follicles >16 mm number on day of hCG administration.
Power to detect a difference between groups Number cycles/group to demonstrate COCP
equivalence Number cycles/group to demonstrate COCP superiority 80% 7 25 85% 7 29 90% 9 33
95% 11 41
To detect equivalence of COCP to luteal estradiol with a power of 90% at an alpha of .05
assuming a 10% attrition rate, we will enroll women into each study group so as to achieve
final number of 10 cycles per treatment group. We assume that an additional 50% decrease in
follicular size would prove COCP superiority. To detect superiority of COCP to luteal
estradiol with a power of 80% at an alpha of 0. 05 assuming 10% attrition rate, we will
enroll women into each study group so as to achieve a final number of 28 cycles per
treatment group. Only newly initiated treatment cycles will be included; only the first
cycle of patients' crossing over to the other treatment group will count toward this
recruitment goal. The second cross over cycle will be compared within patient.
µ1-µ 2 = 4. 9 - 3. 7 mm = 1. 2 (µ1-µ 2)2 = 1. 44 (COCP equivalence) µ1-µ 2 = 1. 8 - 1. 2 mm = 0. 6
(µ1-µ 2)2 = 0. 36 (COCP superiority) SD = б=0. 75 б2 = 0. 5625 2 б2 = 1. 125 α = 0. 05 Zα = 1. 96
(2-sided test) β = 0. 20 1- β = 0. 80 Z β = 0. 84 (1-sided) (Zα +Zβ)2= 7. 84 β =0. 15 1- β =
0. 85 Z β = 1. 03 (1-sided) (Zα +Zβ) 2= 8. 94 β = 0. 10 1- β = 0. 90 Z β = 1. 28 (1-sided) (Zα
+Zβ) 2= 10. 498 β = 0. 05 1- β = 0. 95 Z β = 1. 645 (1-sided) (Zα +Zβ) 2 =12. 996
Calculation: n= (Zα +Zβ)2* 2(б2) / (µ1-µ 2)2
Methods of Analysis
Chi square analysis will be used to compare categorical variables between treatment groups.
Student's t test will be used to compare the mean follicle measurements between treatment
groups.
13. Data & Safety Monitoring:
Adherence and Monitoirng Statement: The Data Safety Monitoring Plan (DSMP) outlined below
will adhere to the protocol approved by the IRB at both Emory University School of Medicine
and Duke University School of Medicine. The Principal investigator (PI) will review all data
collection forms at least annually for completeness and accuracy of the data as well as
protocol compliance. The PI will review this protocol on a continuing basis for subject
safety and include the results of the review in annual progress reports submitted to the
IRB. Adverse events and serious adverse events will also be reviewed by the PI weekly.
Patient Monitoring: Performed by the P. I., the Co-P. I. and/or Co Investigators.
Patient safety data examination, monitoring procedures/oversight: All adverse events (AEs)
will be graded as to their attribution (unrelated to protocol, or possibly, probably, or
definitely related to protocol). Any AE that is reported to either the PI or her designated
research associates by a study subject or by medical staff caring for the subject and which
meets the criteria will be documented as such.
Serious adverse events (SAEs) are predefined as any experience that suggests a significant
hazard, such as events which: a) are fatal, b) are life threatening, c) result in permanent
disability, d) require inpatient hospitalization, or e) involve cancer, a congenital
anomaly, or drug overdose.
Any AEs will be reported to the IRB at Emory and Duke within 24-48 hours of the event. The
standard Emory and Duke IRB reporting guidelines for AE and SAE reporting will be followed.
The investigators and staff will evaluate the SAEs in close coordination with the Emory and
Duke IRB.
Expected adverse events are detailed in the Consent Form and include the following: side
effects of estradiol and combined oral contraceptive pills (breakthrough bleeding, nausea,
headaches, depression, breast tenderness, changes in blood pressure, and increase in risk of
blood clotting); risks of ovulation induction (multiple birth, ovarian hyperstimulation
syndrome, ovarian cyst development, failure to achieve pregnancy); risks of multiple birth
and ovarian hyperstimulation syndrome are less in poor responders regardless of treatment
used; risk of failure to achieve pregnancy is greater in poor responders regardless of
treatment used.
Procedures for minimizing risks: Monitoring with serial ultrasound and blood work will be
used to minimize risks.
Plans for transmission of temporary or permanent suspension actions: Any actions that
mandate temporary or permanent suspension of study will be transmitted to the Emory and Duke
IRB, and, if appropriate, to the FDA and the National Institutes of Health.
Plans for assuring data accuracy and protocol human safety compliance: The above detailed
plans should assure data accuracy and protocol human safety compliance. These include
computerized database management, and IRB oversight and communication. This plan, together
with proposed monitoring by the IRB, should be sufficient without the addition of more
faculty members to constitute a DSMB.
14. Privacy, Data Storage & Confidentiality:
All information and materials will be obtained for research purposes only and the data will
be kept in strict confidence. Confidentiality will be assured by the use of subject codes
rather than personal identifiers. The study database will be secured, and information will
only be entered using subject identifier codes rather than personal identifiers. Electronic
communication will involve only coded, unidentifiable information. All adverse event reports
and annual summaries will not include subject-identifiable material.
Eligibility
Minimum age: 20 Years.
Maximum age: 50 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Antral follicle count < 8
- Antimullerian hormone (AMH) <1. 3
- Follicle stimulating hormone (FSH)>10
- History of follicular dysynchrony or poor response
Exclusion Criteria:
- Menopause
- FSH >40
- Age > 50
- Contraindication to estradiol or COCP (including pre-existing cardiovascular disease,
familial thrombophilia (factor V Leiden), severe hypercholesterolemia, smoker over
age 35) Ovulation induction during month of estradiol treatment
Locations and Contacts
Duke Fertility Center, Durham, North Carolina 27713, United States
Additional Information
Related publications: Stephen EH, Chandra A. Updated projections of infertility in the United States: 1995-2025. Fertil Steril. 1998 Jul;70(1):30-4. Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assisted conception following poor ovarian response to gonadotrophin stimulation. Br J Obstet Gynaecol. 1997 May;104(5):521-7. Review. Fanchin R, Cunha-Filho JS, Schonäuer LM, Kadoch IJ, Cohen-Bacri P, Frydman R. Coordination of early antral follicles by luteal estradiol administration provides a basis for alternative controlled ovarian hyperstimulation regimens. Fertil Steril. 2003 Feb;79(2):316-21. Fanchin R, Cunha-Filho JS, Schonäuer LM, Righini C, de Ziegler D, Frydman R. Luteal estradiol administration strengthens the relationship between day 3 follicle-stimulating hormone and inhibin B levels and ovarian follicular status. Fertil Steril. 2003 Mar;79(3):585-9. Fanchin R, Salomon L, Castelo-Branco A, Olivennes F, Frydman N, Frydman R. Luteal estradiol pre-treatment coordinates follicular growth during controlled ovarian hyperstimulation with GnRH antagonists. Hum Reprod. 2003 Dec;18(12):2698-703. Fanchin R, Castelo Branco A, Kadoch IJ, Hosny G, Bagirova M, Frydman R. Premenstrual administration of gonadotropin-releasing hormone antagonist coordinates early antral follicle sizes and sets up the basis for an innovative concept of controlled ovarian hyperstimulation. Fertil Steril. 2004 Jun;81(6):1554-9. Dragisic KG, Davis OK, Fasouliotis SJ, Rosenwaks Z. Use of a luteal estradiol patch and a gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation for in vitro fertilization in poor responders. Fertil Steril. 2005 Oct;84(4):1023-6. Check JH, Nowroozi K, Chase JS, Nazari A, Shapse D, Vaze M. Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. Fertil Steril. 1990 May;53(5):811-6. Gonen Y, Jacobson W, Casper RF. Gonadotropin suppression with oral contraceptives before in vitro fertilization. Fertil Steril. 1990 Feb;53(2):282-7. Cohen J, Debache C, Solal P, Serkine AM, Achard B, Boujenah A, Pez JP, Paris X, Robert J, Loffredo V. Results of planned in-vitro fertilization programming through the pre-administration of the oestrogen-progesterone combined pill. Hum Reprod. 1987 Jan;2(1):7-9. Biljan MM, Mahutte NG, Dean N, Hemmings R, Bissonnette F, Tan SL. Pretreatment with an oral contraceptive is effective in reducing the incidence of functional ovarian cyst formation during pituitary suppression by gonadotropin-releasing hormone analogues. J Assist Reprod Genet. 1998 Nov;15(10):599-604. Lindheim SR, Barad DH, Witt B, Ditkoff E, Sauer MV. Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation. J Assist Reprod Genet. 1996 Oct;13(9):745-7. Scott RT, Navot D. Enhancement of ovarian responsiveness with microdoses of gonadotropin-releasing hormone agonist during ovulation induction for in vitro fertilization. Fertil Steril. 1994 May;61(5):880-5. Schoolcraft W, Schlenker T, Gee M, Stevens J, Wagley L. Improved controlled ovarian hyperstimulation in poor responder in vitro fertilization patients with a microdose follicle-stimulating hormone flare, growth hormone protocol. Fertil Steril. 1997 Jan;67(1):93-7. Damario MA, Barmat L, Liu HC, Davis OK, Rosenwaks Z. Dual suppression with oral contraceptives and gonadotrophin releasing-hormone agonists improves in-vitro fertilization outcome in high responder patients. Hum Reprod. 1997 Nov;12(11):2359-65. Dumesic DA, Damario MA, Session DR, Famuyide A, Lesnick TG, Thornhill AR, McNeilly AS. Ovarian morphology and serum hormone markers as predictors of ovarian follicle recruitment by gonadotropins for in vitro fertilization. J Clin Endocrinol Metab. 2001 Jun;86(6):2538-43. Mercé LT, Gómez B, Engels V, Bau S, Bajo JM. Intraobserver and interobserver reproducibility of ovarian volume, antral follicle count, and vascularity indices obtained with transvaginal 3-dimensional ultrasonography, power Doppler angiography, and the virtual organ computer-aided analysis imaging program. J Ultrasound Med. 2005 Sep;24(9):1279-87. Scheffer GJ, Broekmans FJ, Bancsi LF, Habbema JD, Looman CW, Te Velde ER. Quantitative transvaginal two- and three-dimensional sonography of the ovaries: reproducibility of antral follicle counts. Ultrasound Obstet Gynecol. 2002 Sep;20(3):270-5. Pöhl M, Hohlagschwandtner M, Obruca A, Poschalko G, Weigert M, Feichtinger W. Number and size of antral follicles as predictive factors in vitro fertilization and embryo transfer. J Assist Reprod Genet. 2000 Jul;17(6):315-8. Tomas C, Nuojua-Huttunen S, Martikainen H. Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization. Hum Reprod. 1997 Feb;12(2):220-3. Yong PY, Baird DT, Thong KJ, McNeilly AS, Anderson RA. Prospective analysis of the relationships between the ovarian follicle cohort and basal FSH concentration, the inhibin response to exogenous FSH and ovarian follicle number at different stages of the normal menstrual cycle and after pituitary down-regulation. Hum Reprod. 2003 Jan;18(1):35-44. Fanchin R, Louafi N, Méndez Lozano DH, Frydman N, Frydman R, Taieb J. Per-follicle measurements indicate that anti-müllerian hormone secretion is modulated by the extent of follicular development and luteinization and may reflect qualitatively the ovarian follicular status. Fertil Steril. 2005 Jul;84(1):167-73. Fanchin R, Méndez Lozano DH, Louafi N, Achour-Frydman N, Frydman R, Taieb J. Dynamics of serum anti-Müllerian hormone levels during the luteal phase of controlled ovarian hyperstimulation. Hum Reprod. 2005 Mar;20(3):747-51. Epub 2004 Dec 23. Fanchin R, Taieb J, Lozano DH, Ducot B, Frydman R, Bouyer J. High reproducibility of serum anti-Mullerian hormone measurements suggests a multi-staged follicular secretion and strengthens its role in the assessment of ovarian follicular status. Hum Reprod. 2005 Apr;20(4):923-7. Epub 2005 Jan 7.
Starting date: October 2010
Last updated: November 19, 2012
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