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Ovarian Reserve and Assisted Reproduction
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Treatment success in IVF-ICSI is mainly limited by female age, but differences in ovarian reserve (OR; the remaining pool of oocytes and their quality) between individuals modify treatment prerequisites among women of similar age. OR may be assessed by OR tests (ORTs). The main aims of this work were to study menstrual cycle length (MCL), basal levels of circulating gonadotrophins, antral follicle count (AFC) and serum Anti-Müllerian hormone (AMH) levels and their associations with and prognostic capacities regarding IVF-ICSI outcome in large cohorts of unselected women.

Age-adjusted MCL was positively and linearly associated with pregnancy rates (PRs), live-birth rates (LBRs) and ovarian response to controlled ovarian hyperstimulation. An MCL of >34 days almost doubled the LBR compared with an MCL of <26 days.

The grouped variable ‘combined FSH and LH levels’ was superior to both individual gonadotrophin levels and the LH:FSH ratio. The highest mean PR was seen in connection with a combination of FSH <6.7 U/l with LH >4.9 U/l; PRs were lowest when FSH-LH levels were opposite to this (high-low) and intermediate when FSH-LH levels were low-low or high-high. Associations with LBR and ovarian response were similar as those for PR.

AFCs and serum AMH levels were positively and log-linearly associated with PR, LBR and ovarian response. Success rates levelled out above AFC 30 or AMH 5 ng/ml. Treatment outcome was superior among women with polycystic ovaries.

Among the studied ORTs, logAFC and logAMH concentration correlated most strongly. After multivariate testing, entering all studied ORTs, AMH and female age remained independently associated with LBR. AMH + AFC + age predicted both poor and excessive ovarian responses with high accuracy.

Adjusting for age and oocyte yield, all ORTs remained significant for LBR, implying that ORTs also capture information on oocyte quality.

In conclusion, measures of OR are strongly associated with PR, LBR and ovarian response in a log-linear fashion, and partly reflect oocyte quality. The OR spectrum is continuous, from small ‘oligofollicular’ ovaries (the low extreme) to polycystic ovaries (the high extreme). Among the studied ORTs, AMH together with age provide the most powerful basal estimate for IVF/ICSI outcome.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. , 88 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 865
Keyword [en]
AFC, AMH, anti-Müllerian hormone, antral follicle count, follicle-stimulating hormone, FSH, ICSI, infertility, intracytoplasmic sperm injection, in vitro fertilization, IVF, LH, live birth, luteinizing hormone, menstrual cycle, menstrual cycle length, ovarian reserve, pregnancy, reproductive endocrinology, reproductive technology
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-192998ISBN: 978-91-554-8592-4 (print)OAI: oai:DiVA.org:uu-192998DiVA: diva2:602740
Public defence
2013-03-22, Sal IX, Universitetshuset, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2013-02-28 Created: 2013-01-28 Last updated: 2013-03-05Bibliographically approved
List of papers
1. Menstrual cycle length is an age-independent marker of female fertility: results from 6271 treatment cycles of in vitro fertilization
Open this publication in new window or tab >>Menstrual cycle length is an age-independent marker of female fertility: results from 6271 treatment cycles of in vitro fertilization
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2008 (English)In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 90, no 5, 1656-1661 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate whether menstrual cycle length correlates with success rates at IVF/intracytoplasmic sperm injection (ICSI) and could be used as a marker of ovarian reserve. DESIGN: Prospective observational study. SETTING: Private infertility centre. PATIENT(S): A total of 6271 IVF/ICSI treatment cycles. INTERVENTION(S): Self-reported mean number of menstrual days during the last year was recorded before initiation of IVF/ICSI treatment. MAIN OUTCOME MEASURE(S): Relations between menstrual cycle length and pregnancy and delivery rates. RESULT(S): Increasing age was associated with a subtle shortening of mean menstrual cycle length. Menstrual cycle length correlated linearly with pregnancy and delivery rates, even after age adjustment. The chance of delivery after IVF/ICSI was almost doubled for women with a menstrual cycle length >34 days compared with women with a menstrual cycle length <26 days. Menstrual cycle length was also significantly associated with ovarian response to FSH/hMG stimulation and embryo quality. CONCLUSION(S): Mean menstrual cycle length is highly related to success rates in assisted reproduction, independently of age. A precise menstrual cycle history could be used as a simple marker of ovarian reserve.

Keyword
Fecundity, female age, infertility, IVF, menstrual cycle, ovarian reserve
Identifiers
urn:nbn:se:uu:diva-107097 (URN)10.1016/j.fertnstert.2007.09.036 (DOI)000260752000015 ()18155201 (PubMedID)
Available from: 2009-07-16 Created: 2009-07-16 Last updated: 2017-12-13Bibliographically approved
2. High basal LH levels in combination with low basal FSH levels are associated with high success rates at assisted reproduction
Open this publication in new window or tab >>High basal LH levels in combination with low basal FSH levels are associated with high success rates at assisted reproduction
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2009 (English)In: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 24, no 11, 2755-2759 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND The objective of this study was to evaluate the associations of basal gonadotrophins with pregnancy and delivery rates at IVF/ICSI. METHODS A prospective observational study was conducted at a university-affiliated private infertility centre. Patients were 745 women, who underwent 1328 IVF/ICSI treatment cycles. Basal FSH, basal LH and combinations of FSH and LH versus treatment data and pregnancy and delivery rates were measured. RESULTS Combinations of FSH and LH gave significantly better information than the LH:FSH ratio, or each gonadotrophin alone: highest mean pregnancy rate (39%) was achieved in women with low FSH (<6.7 U/l) and with high LH levels (>4.9 U/l), whereas pregnancy rate was lowest (22%) in women with high FSH and low LH levels. Pregnancy rates were intermediate (27-28%) if FSH and LH were either both low or both high (P for trend = 0.0004). Associations to delivery rates and measures of ovarian response and embryo quality followed the same pattern. CONCLUSIONS Basal LH modifies and improves the information given by basal FSH alone. Low FSH level combined with high LH probably reflects a well-preserved ovarian reserve and is associated with the highest success rates at IVF/ICSI.

Keyword
FSH, infertility, IVF, ICSI outcome, luteinizing hormone, ovarian reserve
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-107635 (URN)10.1093/humrep/dep254 (DOI)000271107700013 ()19617206 (PubMedID)
Available from: 2009-08-20 Created: 2009-08-20 Last updated: 2017-12-13Bibliographically approved
3. Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries
Open this publication in new window or tab >>Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries
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2011 (English)In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, no 3, 594-599 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. Design: Prospective observational study. Setting: University-affiliated private infertility center. Patient(s): 2,092 women undergoing 4,308 IVF-ICSI cycles. Intervention(s): AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. Main Outcome Measure(s): Pregnancy rate, live-birth rate, and stimulation outcome parameters. Result(s): The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC similar to 30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. Conclusion(s): Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity.

Keyword
AFC, antral follicle count, infertility, IVF, ovarian reserve, PCO
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-158865 (URN)10.1016/j.fertnstert.2011.06.071 (DOI)000294417000026 ()
Available from: 2011-09-20 Created: 2011-09-19 Last updated: 2017-12-08Bibliographically approved
4. Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction
Open this publication in new window or tab >>Antimüllerian hormone levels are strongly associated with live-birth rates after assisted reproduction
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2013 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 3, 1107-1114 p.Article in journal (Refereed) Published
Abstract [en]

Context: Previous studies have suggested that antimullerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. Objective: The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. Design: The study was a prospective cohort study between April 2008 and June 2011. Setting: The study was done at a university-affiliated private infertility center. Patients: The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. Intervention(s): AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. Main Outcome Measures: Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured. Results: AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH < 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH > 2.94 ng/mL (75th percentile), P-trend < .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. Conclusions: AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.

Keyword
Anti-Mullerian Hormone, Polycystic-Ovary-Syndrome, Antral Follicle Counts, Menstrual-Cycle, Women, Ivf; Reserve, Age, Stimulatio, Embryo
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-192987 (URN)10.1210/jc.2012-3676 (DOI)000316417200060 ()23408576 (PubMedID)
Available from: 2013-01-28 Created: 2013-01-28 Last updated: 2017-12-06Bibliographically approved
5. A comparison of four different ovarian reserve tests (ORT) for predicting the ovarian response and chance of live birth after IVF-ICSI treatment
Open this publication in new window or tab >>A comparison of four different ovarian reserve tests (ORT) for predicting the ovarian response and chance of live birth after IVF-ICSI treatment
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(English)Manuscript (preprint) (Other academic)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-192988 (URN)
Available from: 2013-01-28 Created: 2013-01-28 Last updated: 2013-03-05

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