| dc.description.abstract | Ovarian reserve is a key component influencing reproductive function and fertility. Serum anti-Mullerian hormone (AMH) and antral follicle count (AFC) are established quantitative markers of ovarian reserve. The overall aim of this thesis comprising four work packages was to study the role of AMH and AFC on different aspects of fertility and fertility treatment. Their specific objectives were:
1) To compare per-follicle AMH production in various phenotypes of women with polycystic ovary syndrome (PCOS) and with isolated polycystic ovarian morphology (PCOM).
2) To assess the effect of cigarette smoking on quantitative ovarian reserve markers in sub-fertile women, validating self-reported smoking behavior using biomarkers (breath carbon monoxide levels and urine cotinine levels).
3) To assess the effect of treatment with myo-inositol (MI)/di-chiro inositol (DCI) compared to no treatment, placebo or other treatment on markers of ovarian reserve in women with PCOS combining data from published literature.
4) To assess the association between ovarian reserve markers and embryo quality in women undergoing IVF/ICSI treatment using time lapse imaging technology.
The work for the thesis included primary research consisting of three single-centre, observational, cross-sectional studies and one evidence synthesis based on a systematic review of published literature. The study population was subfertile women seeking fertility treatment, and the primary outcome measure was ovarian reserve assessed by serum AMH and AFC.
A significantly greater per-follicle AMH production observed in anovulatory phenotypes of PCOS may represent a heightened physiological role of AMH leading to ovulatory dysfunction. In our study, exposure to cigarette smoking in women 35 years seeking fertility treatment did not significantly change the antral follicle pool. The biomarkers of ovarian reserve were not significantly associated with the biomarkers of smoking or lifetime smoking exposure.
Based on currently available data, our systematic review reported that evidence is lacking for an effect of inositols on altering ovarian reserve markers or subsequent outcomes following IVF/ICSI treatment.
We found no significant association between ovarian reserve markers and embryo quality in women undergoing IVF/ICSI treatment. Their positive association with improved pregnancy outcomes following IVF/ICSI is most likely indirect, through the increased numbers of oocytes retrieved. | en_US |
| dc.description.popularabstract | Every woman is born with a definite number of eggs at birth - approximately two million in number. These are gradually used until the age of menopause when they are depleted. The egg reserve hence decreases with increasing age. The body does not make new eggs over a lifetime and each woman’s egg reserve is thus pre-determined. The egg reserve can be influenced by several factors which include a person’s genetic make-up, their lifestyle and other factors such as diseases and their treatments. The egg reserve is a key component influencing fertility. The number of eggs at any time point may be estimated by measuring a hormone called anti-Mullerian hormone (AMH) or using an ultrasound scan of the ovary to count the number of visible egg sacs. This is called the antral follicle count (AFC).
The overall aim of this thesis which was made up of four work packages was to study the role of AMH and AFC as surrogate markers of the egg reserve on different aspects of fertility and fertility treatment. The specific aims of each work package were:
1) To compare the AMH hormone production per egg in the various subtypes of women who present with a condition called polycystic ovary syndrome (PCOS). Women with PCOS may present with different complaints/symptoms and we wanted to see if AMH production was different depending on the presenting complaint.
2) To assess the effect of cigarette smoking on the egg reserve in women with fertility problems, and to confirm if self-reported smoking behavior by women matched with more unbiased tests such as breath levels of carbon monoxide and urine levels of cotinine which are both products of cigarette smoke.
3) To assess the effect of treatment with a medication called myo-inositol compared to no treatment, dummy treatment or treatment with other similar medication on hormone and ultrasound markers of egg reserve in women with PCOS, pooling information from previously published studies.
4) To assess the association between egg reserve and embryo quality using a specialised technology called time lapse imaging in women undergoing IVF fertility treatment.
The work for the thesis included collecting socio-demographic and clinical information from women attending the fertility clinic of the hospital and also pooling information from previously published studies. The information for each woman was collected at a single time point to obtain a snapshot view of their egg reserve at that time using blood test to measure AMH and AFC using ultrasound scans. We also collected information pertinent to the study question such as information on smoking or quality of embryos during fertility treatment, age, height, weight and other clinical details which could impact on the results and conclusions for the studies and adjusted for their influences while interpreting the findings.
We found significantly higher AMH production in those women with PCOS who presented with irregular periods (suggesting that these women were not releasing their eggs regularly/not ovulating) as compared to those with regular periods. We think that in these women, this may be an exaggeration of the normal role of this hormone in the body resulting in failure to regularly ovulate/release an egg. In another study, we found that exposure to cigarette smoking in women 35 years or less was not associated with a significant change in the egg reserve compared to nonsmokers. The markers of egg reserve were neither significantly associated with the breath carbon monoxide or urine cotinine levels nor the lifetime smoking exposure.
Our review of the effects of myo-inositol in women with PCOS reported that there was not adequate evidence to show that inositols changed egg reserve markers or subsequent outcomes following fertility treatment.
We found no meaningful direct association between egg reserve (number of eggs) and embryo quality in women undergoing IVF treatment. We found a positive association between the egg reserve and the chance of getting pregnant following IVF treatment. However, this effect is most likely to be indirect because of the increased numbers rather than better quality of the eggs. | en_US |
| dc.relation.haspart | <p>Paper I: Bhide P, Kulkarni A, Dilgil M, Dhir P, Shah A, Gudi A, Homburg R. Phenotypic variation in anti-Mullerian hormone (AMH) production per follicle in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovarian morphology (PCOM): an observational cross-sectional study. Gynecol Endocrinol. 2017 Oct;33(10):801-806. Published version not available in Munin due to publisher’s restrictions. Published version available at <a href=https://doi.org/10.1080/09513590.2017.1320377>https://doi.org/10.1080/09513590.2017.1320377</a>.
<p>Paper II: Bhide, P., Escriba, M., Srikantharajah, A., Joshi, H., Gudi, A., Shah, A., Acharya, G. & Homburg, R. (2017). Anti-Mullerian hormone (AMH) and embryo quality assessed by time-lapse imaging (TLI): a cross-sectional observational study. <i>Archives of Gynecology and Obstetrics, 296</i>(3), 583-587. Also available at <a href=https://doi.org/10.1007/s00404-017-4453-2>https://doi.org/10.1007/s00404-017-4453-2</a>.
<p>Paper III: Bhide, P., Pundir, J., Gudi, A., Shah, A., Homburg, R. & Acharya, G. (2019). The effect of myo‐inositol/di‐chiro‐inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta‐analysis. <i>Acta Obstetricia et Gynecologica Scandinavica, 98</i>, 1235‐ 1244. Also available at <a href=https://doi.org/10.1111/aogs.13625>https://doi.org/10.1111/aogs.13625</a>.
<p>Paper IV: Bhide, P., Timlick, E., Kulkarni, A., Gudi, A., Shah, A., Homburg, R. & Acharya, G. Effect of cigarette smoking on serum anti-Mullerian hormone and antral follicle count in women seeking fertility treatment. (Submitted manuscript). | en_US |
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