Stephen Keay - Academia.edu (original) (raw)

Papers by Stephen Keay

Research paper thumbnail of The practical implications of a raised serum FSH and age on the risk of IVF treatment cancellation due to a poor ovarian response

Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related t... more Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related to ovarian reserve. This study addresses the likelihood of cancellation of IVF treatment due to a poor ovarian response utilising both basal serum FSH and woman's age. Methods : A prospective cohort of 536 infertile but ovulating women were studied in their first cycle of IVF treatment. Standardised methods of pituitary desensitisation and ovarian stimulation prior to IVF treatment were employed. Treatment cycles cancelled due to a poor ovarian response to gonadotrophins were studied. A series of logistic regression models were used to explore the probabilities of cancellation in relation to age and FSH. Results : Both age and basal serum FSH levels were independently associated with the risk of treatment cancellation. A low risk of treatment cancellation was observed in women under the age of 35 irrespective of serum FSH, however in older women the risk of treatment cancellation was most likely in women with a high FSH. Conclusions : In combination both age and FSH may serve as a valuable indicator of poor ovarian response leading to treatment cancellation. However, among older women FSH has particular importance, while less so in younger women with regular menstrual cycles.

Research paper thumbnail of Endometrial changes caused by tamoxifen

Eur J Cancer, 1999

The ATAC trial is a double blind study, designed to compare the efficacy and safety of tamoxifen ... more The ATAC trial is a double blind study, designed to compare the efficacy and safety of tamoxifen alone, Arimidex (anastrozole) alone, and the combination of tamoxifen plus anastrozole, as adjuvant treatment in post-menopausal women with early breast cancer, who have completed primary therapy. Treatment will be for 5 years or until first recurrence. The dose of tamoxifen is 20 mgs od and anastrozole 1 mg od.

Research paper thumbnail of Periovulatory human oocytes, cumulus cells, and ovarian leukocytes express type 1 but not type 2 11β-hydroxysteroid dehydrogenase RNA

Fertility and Sterility, Apr 30, 2000

To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte... more To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte retrieval, the presence of 11␤-hydroxysteroid dehydrogenase (HSD) messenger (m)RNA transcripts in oocytes; cumulus cells; granulosa cells; and CD45 ϩ , CD15 ϩ leukocytes was assessed semiquantitatively. Design: Controlled study using semiquantitative assessment of 11␤-HSD mRNA. Setting: University IVF center. Patient(s): Twenty-six patients undergoing controlled ovarian hyperstimulation for assisted conception. Intervention(s): Metaphase II oocytes; cumulus cells; granulosa cells, and CD45 ϩ , CD15 ϩ leukocytes from individual follicular fluid aspirates. Main Outcome Measures: Semiquantitative analysis of PCR products after total RNA extraction and complementary DNA synthesis. Result(s): Periovulatory human oocytes; cumulus cells; CD45 ϩ , CD15 ϩ leukocytes; and granulosa cells consistently express type 1 but not type 2 11␤-HSD mRNA. Expression of mRNA is greatest in cumulus cells. Type 1 11␤-HSD mRNA expression varies considerably in all cell types and among individual follicles and patients.

Research paper thumbnail of Website reviews @ TOG

The Obstetrician & Gynaecologist, 2008

Research paper thumbnail of Laparoscopic management of interstitial pregnancy with automatic stapler

Case Reports, 2012

A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic ... more A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic pain in her seventh week of pregnancy. She had a transvaginal ultrasound. Unruptured live twin tubal ectopic pregnancy was diagnosed on. Diagnostic laparoscopy revealed an unruptured left interstitial ectopic pregnancy. The interstitial tubal pregnancy was removed by laparoscopic automatic stapler with minimal blood loss. The patient had an uneventful recovery to health.

Research paper thumbnail of Website reviews @ TOG

The Obstetrician & Gynaecologist, 2010

Research paper thumbnail of Stage Ia endometrial carcinoma diagnosed on removal of an IUD

Journal of Family Planning and Reproductive Health Care, 2001

This is a case report of a 49-year-old woman who presented with offensive vaginal discharge. Her ... more This is a case report of a 49-year-old woman who presented with offensive vaginal discharge. Her Lippes loop IUD was removed and discovered to have suspicious material attached. Histology report was of endometrial carcinoma. This is the first report of an endometrial carcinoma being completely removed along with an IUD.

Research paper thumbnail of Increased Visfatin Messenger Ribonucleic Acid and Protein Levels in Adipose Tissue and Adipocytes in Women with Polycystic Ovary Syndrome: Parallel Increase in Plasma Visfatin

The Journal of Clinical Endocrinology & Metabolism, 2006

Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistan... more Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistance (IR) and obesity. Recent studies have shown that plasma levels of the insulin-mimetic adipokine visfatin increase with obesity. Currently, no data exist on the relative expression of visfatin in either plasma or adipose tissue of PCOS women. We investigated the mRNA expression of visfatin from sc and omental (om) adipose tissue and sc adipocytes in women with PCOS compared with matched normal women, as well as visfatin protein in adipose tissue; plasma visfatin was also assessed. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. Biochemical measurements were performed. There was significant up-regulation of visfatin mRNA in both sc (P < 0.05) and om (P < 0.05) adipose tissue of PCOS women, when compared with normal controls; these findings were also reflected in isolated sc adipocytes (PCOS > controls; P < 0.05). In addition to elevated plasma visfatin levels in women with PCOS (mean +/- sd, 30.2 +/- 10.4 vs. 11.2 +/- 6.2 ng/ml; P < 0.01) when compared with normal controls, visfatin protein levels were significantly greater in both sc and om adipose tissue of PCOS women (P < 0.05 and P < 0.01, respectively). The precise reason for the up-regulation of visfatin seen in women with PCOS, a proinflammatory state, is unknown. Additional studies are needed to clarify the potential role of visfatin in the pathophysiology of PCOS.

Research paper thumbnail of The Practical Implications of a Raised Serum FSH and Age on the Risk of IVF Treatment Cancellation Due to a Poor Ovarian Response

Journal of Assisted Reproduction and Genetics, 2000

Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related t... more Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related to ovarian reserve. This study addresses the likelihood of cancellation of IVF treatment due to a poor ovarian response utilising both basal serum FSH and woman's age. Methods : A prospective cohort of 536 infertile but ovulating women were studied in their first cycle of IVF treatment. Standardised methods of pituitary desensitisation and ovarian stimulation prior to IVF treatment were employed. Treatment cycles cancelled due to a poor ovarian response to gonadotrophins were studied. A series of logistic regression models were used to explore the probabilities of cancellation in relation to age and FSH. Results : Both age and basal serum FSH levels were independently associated with the risk of treatment cancellation. A low risk of treatment cancellation was observed in women under the age of 35 irrespective of serum FSH, however in older women the risk of treatment cancellation was most likely in women with a high FSH. Conclusions : In combination both age and FSH may serve as a valuable indicator of poor ovarian response leading to treatment cancellation. However, among older women FSH has particular importance, while less so in younger women with regular menstrual cycles.

Research paper thumbnail of Low-dose dexamethasone augments the ovarian response to exogenous gonadotrophins leading to a reduction in cycle cancellation rate in a standard IVF programme

Human Reproduction, 2001

BACKGROUND: Cancellation of assisted conception cycles because of poor ovarian response to gonado... more BACKGROUND: Cancellation of assisted conception cycles because of poor ovarian response to gonadotrophins is a significant problem in assisted reproduction. Various adjuvant treatments have been suggested to improve responsiveness. This study reports on the potential benefits of low dose dexamethasone. METHODS: Patients <40 years of age were invited to participate in a twin centre prospective double blind randomized placebo controlled study. A total of 290 patients were recruited and computer randomized using sealed envelopes to receive either 1 mg dexamethasone (n ϭ 145) or placebo tablets (n ⍧ 145) in addition to a standard long protocol gonadotrophinreleasing hormone analogue with gonadotrophin stimulation regime. RESULTS: A significantly lower cancellation rate for poor ovarian response was observed in the dexamethasone group compared with controls (2.8 versus 12.4% respectively, P < 0.002). Further comparisons between the dexamethasone group and controls were made of median fertilization rates (60 versus 61% respectively, NS), implantation rates (16.3 versus 11.6% respectively, NS) and pregnancy rate per cycle started (26.9 versus 17.2%, NS). The benefit was apparent in patients both with polycystic and normal ovaries. CONCLUSION: Low dose dexamethasone co-treatment reduces the incidence of poor ovarian response. It may increase clinical pregnancy rates and should be considered for inclusion in stimulation regimes to optimize ovarian response.

Research paper thumbnail of Higher cortisol:cortisone ratios in the preovulatory follicle of completely unstimulated IVF cycles indicate oocytes with increased pregnancy potential

Human Reproduction, 2002

BACKGROUND: Conception following gonadotrophin-stimulated IVF and embryo transfer has been associ... more BACKGROUND: Conception following gonadotrophin-stimulated IVF and embryo transfer has been associated with a higher intrafollicular cortisol:cortisone ratio and decreased metabolism of cortisol to cortisone. The role of glucocorticoids in human oocyte maturation is not fully understood, but active glucocorticoid (cortisol) may be important. This study relates intrafollicular cortisol and cortisone concentrations to oocyte fertilization and embryo implantation in unstimulated cycles. METHODS: Patients aged <40 years with favourable sperm underwent unstimulated IVF-embryo transfer. Study 1 related intrafollicular cortisol levels to oocyte and IVF outcome: (i) fertilized, pregnant (n ⍧ 9); (ii) fertilized, not pregnant (n ⍧ 21); and (iii) unfertilized (n ⍧ 12). Study 2 was a case-control study of 27 patients (same outcome groups of equal size) which measured intrafollicular cortisol, cortisone and the cortisol:cortisone ratio. RESULTS: Conception cycles demonstrated higher cortisol concentrations compared with the fertilized group (study 1) [median (95% confidence interval): 299 (249-330) versus 227 nmol/l (185-261); P < 0.05] and higher cortisol:cortisone ratios when compared with the unfertilized group (study 2) [7.38 (5.23-9.19) versus 3.56 (1.75-7.46) respectively; P ⍧ 0.02]. Of the women with cortisol:cortisone ratios greater than the outcome independent mean of 5.90, 58% conceived compared with only 13% with ratios Ͻ5.90 (P Ͻ 0.02). CONCLUSION: Higher cortisol:cortisone ratios in conception cycles suggest that active glucocorticoid may be important for final oocyte maturation and embryo implantation in unstimulated cycles.

Research paper thumbnail of Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome

Research paper thumbnail of Biological versus chronological ageing of oocytes, distinguishable by raised FSH levels in relation to the success of IVF treatment

Human Reproduction, 2002

BACKGROUND: The present study addresses the issue of biological ageing of the oocyte (as indicate... more BACKGROUND: The present study addresses the issue of biological ageing of the oocyte (as indicated by basal serum FSH levels) versus chronological ageing. METHODS: 1019 infertile but ovulating women were studied in their first cycle of IVF treatment. A series of logistic regression models were developed to assess statistical significance of effects of age and FSH on implantation rates and live babies born. RESULTS: The number of oocytes retrieved and embryos available for transfer declined with increasing age and basal serum FSH concentrations. Fertilizing ability of oocytes increased with advancing age but was not affected by FSH concentrations. Although the number of oocytes or embryos available for transfer had no independent effect on implantation rates, the implanting ability of fertilized oocytes (embryos) was inversely related to increasing age and independently to FSH. The chance of a baby being born, however, was determined more by age than by serum FSH. CONCLUSIONS: Ovarian ageing affecting oocyte quality and fecundity can occur independently of chronological age. This has important practical implications whereby serum basal FSH measurement may be a valuable prognostic index, though chronological age remains important.

Research paper thumbnail of Any effect of adjuvant low dose prednisolone on follicular development and embryo implantation may be masked by the concomitant use of aspirin

Research paper thumbnail of Different aetiological mechanisms for unexplained and endometriosis-associated infertility cannot be inferred from unstimulated IVF cycles using HCG to induce ovulation

Research paper thumbnail of Electronic transfer of mandatory infertility information: Survey of opinion of licensed treatment centres

Human Fertility, 2000

1. Hum Fertil (Camb). 2000;3(1):11-12. Electronic transfer of mandatory infertility information: ... more 1. Hum Fertil (Camb). 2000;3(1):11-12. Electronic transfer of mandatory infertility information: survey of opinion of licensed treatment centres. Keay SD, Corrigan E, Wardle PG, Hull MG, Jenkins JM. Centre for Reproductive Medicine ...

Research paper thumbnail of Poor ovarian response to gonadotrophin stimulation — The role of adjuvant treatments

Human Fertility, 2002

Poor ovarian response to gonadotrophin stimulation represents a clinical problem in in vitro fert... more Poor ovarian response to gonadotrophin stimulation represents a clinical problem in in vitro fertilization practice. Women showing poor ovarian response are a heterogeneous group, many of whom have a reduced ovarian reserve and consequently a lower pregnancy potential. Various management strategies have been proposed to improve ovarian response to gonadotrophins, but these have met with limited success. Adjuvant treatments aim to potentiate the effect of exogenous follicle-stimulating hormone. In separate, randomized, placebo-controlled trials low-dose dexamethasone and aspirin have been shown to reduce the incidence of poor response in an initial stimulation cycle. Preliminary studies using pyridostigmine and L-arginine in established poor responders are encouraging but require confirmation in adequately powered studies. Evidence from randomized controlled trials does not support the use of adjuvant growth hormone or growth hormone-releasing hormone in poor responders without overt growth hormone deficiency. The mechanisms of action of adjuvant treatments require further investigation.

Research paper thumbnail of Distinction between early and late ovarian hyperstimulation syndrome

Fertility and Sterility, 2000

Objective: To compare patient and cycle characteristics among three study groups: early ovarian h... more Objective: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. Design: Prospective observational study. Setting: University assisted conception service. Patient(s): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. Intervention: None. Main Outcome Measure(s): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E 2 ) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. Result(s): Women with early OHSS had significantly higher serum E 2 levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E 2 and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. Conclusion(s): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events. (Fertil Steril 2000;73:901-7.

Research paper thumbnail of Ovarian reserve and a slightly different perspective

Fertility and Sterility, 2004

Research paper thumbnail of Adjunctive use of dexamethasome in Clomid resistant patients

Fertility and Sterility, 2003

Research paper thumbnail of The practical implications of a raised serum FSH and age on the risk of IVF treatment cancellation due to a poor ovarian response

Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related t... more Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related to ovarian reserve. This study addresses the likelihood of cancellation of IVF treatment due to a poor ovarian response utilising both basal serum FSH and woman's age. Methods : A prospective cohort of 536 infertile but ovulating women were studied in their first cycle of IVF treatment. Standardised methods of pituitary desensitisation and ovarian stimulation prior to IVF treatment were employed. Treatment cycles cancelled due to a poor ovarian response to gonadotrophins were studied. A series of logistic regression models were used to explore the probabilities of cancellation in relation to age and FSH. Results : Both age and basal serum FSH levels were independently associated with the risk of treatment cancellation. A low risk of treatment cancellation was observed in women under the age of 35 irrespective of serum FSH, however in older women the risk of treatment cancellation was most likely in women with a high FSH. Conclusions : In combination both age and FSH may serve as a valuable indicator of poor ovarian response leading to treatment cancellation. However, among older women FSH has particular importance, while less so in younger women with regular menstrual cycles.

Research paper thumbnail of Endometrial changes caused by tamoxifen

Eur J Cancer, 1999

The ATAC trial is a double blind study, designed to compare the efficacy and safety of tamoxifen ... more The ATAC trial is a double blind study, designed to compare the efficacy and safety of tamoxifen alone, Arimidex (anastrozole) alone, and the combination of tamoxifen plus anastrozole, as adjuvant treatment in post-menopausal women with early breast cancer, who have completed primary therapy. Treatment will be for 5 years or until first recurrence. The dose of tamoxifen is 20 mgs od and anastrozole 1 mg od.

Research paper thumbnail of Periovulatory human oocytes, cumulus cells, and ovarian leukocytes express type 1 but not type 2 11β-hydroxysteroid dehydrogenase RNA

Fertility and Sterility, Apr 30, 2000

To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte... more To further elucidate cortisol metabolism in the follicular microenvironment at the time of oocyte retrieval, the presence of 11␤-hydroxysteroid dehydrogenase (HSD) messenger (m)RNA transcripts in oocytes; cumulus cells; granulosa cells; and CD45 ϩ , CD15 ϩ leukocytes was assessed semiquantitatively. Design: Controlled study using semiquantitative assessment of 11␤-HSD mRNA. Setting: University IVF center. Patient(s): Twenty-six patients undergoing controlled ovarian hyperstimulation for assisted conception. Intervention(s): Metaphase II oocytes; cumulus cells; granulosa cells, and CD45 ϩ , CD15 ϩ leukocytes from individual follicular fluid aspirates. Main Outcome Measures: Semiquantitative analysis of PCR products after total RNA extraction and complementary DNA synthesis. Result(s): Periovulatory human oocytes; cumulus cells; CD45 ϩ , CD15 ϩ leukocytes; and granulosa cells consistently express type 1 but not type 2 11␤-HSD mRNA. Expression of mRNA is greatest in cumulus cells. Type 1 11␤-HSD mRNA expression varies considerably in all cell types and among individual follicles and patients.

Research paper thumbnail of Website reviews @ TOG

The Obstetrician & Gynaecologist, 2008

Research paper thumbnail of Laparoscopic management of interstitial pregnancy with automatic stapler

Case Reports, 2012

A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic ... more A 36-year-old woman was referred by general practitioner to the early pregnancy unit with pelvic pain in her seventh week of pregnancy. She had a transvaginal ultrasound. Unruptured live twin tubal ectopic pregnancy was diagnosed on. Diagnostic laparoscopy revealed an unruptured left interstitial ectopic pregnancy. The interstitial tubal pregnancy was removed by laparoscopic automatic stapler with minimal blood loss. The patient had an uneventful recovery to health.

Research paper thumbnail of Website reviews @ TOG

The Obstetrician & Gynaecologist, 2010

Research paper thumbnail of Stage Ia endometrial carcinoma diagnosed on removal of an IUD

Journal of Family Planning and Reproductive Health Care, 2001

This is a case report of a 49-year-old woman who presented with offensive vaginal discharge. Her ... more This is a case report of a 49-year-old woman who presented with offensive vaginal discharge. Her Lippes loop IUD was removed and discovered to have suspicious material attached. Histology report was of endometrial carcinoma. This is the first report of an endometrial carcinoma being completely removed along with an IUD.

Research paper thumbnail of Increased Visfatin Messenger Ribonucleic Acid and Protein Levels in Adipose Tissue and Adipocytes in Women with Polycystic Ovary Syndrome: Parallel Increase in Plasma Visfatin

The Journal of Clinical Endocrinology & Metabolism, 2006

Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistan... more Polycystic ovary syndrome (PCOS) is a multifaceted metabolic disease linked with insulin resistance (IR) and obesity. Recent studies have shown that plasma levels of the insulin-mimetic adipokine visfatin increase with obesity. Currently, no data exist on the relative expression of visfatin in either plasma or adipose tissue of PCOS women. We investigated the mRNA expression of visfatin from sc and omental (om) adipose tissue and sc adipocytes in women with PCOS compared with matched normal women, as well as visfatin protein in adipose tissue; plasma visfatin was also assessed. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of visfatin. Biochemical measurements were performed. There was significant up-regulation of visfatin mRNA in both sc (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and om (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) adipose tissue of PCOS women, when compared with normal controls; these findings were also reflected in isolated sc adipocytes (PCOS &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; controls; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In addition to elevated plasma visfatin levels in women with PCOS (mean +/- sd, 30.2 +/- 10.4 vs. 11.2 +/- 6.2 ng/ml; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) when compared with normal controls, visfatin protein levels were significantly greater in both sc and om adipose tissue of PCOS women (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 and P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, respectively). The precise reason for the up-regulation of visfatin seen in women with PCOS, a proinflammatory state, is unknown. Additional studies are needed to clarify the potential role of visfatin in the pathophysiology of PCOS.

Research paper thumbnail of The Practical Implications of a Raised Serum FSH and Age on the Risk of IVF Treatment Cancellation Due to a Poor Ovarian Response

Journal of Assisted Reproduction and Genetics, 2000

Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related t... more Purpose : Chronological age, or biological age as indicated by elevated FSH levels, are related to ovarian reserve. This study addresses the likelihood of cancellation of IVF treatment due to a poor ovarian response utilising both basal serum FSH and woman's age. Methods : A prospective cohort of 536 infertile but ovulating women were studied in their first cycle of IVF treatment. Standardised methods of pituitary desensitisation and ovarian stimulation prior to IVF treatment were employed. Treatment cycles cancelled due to a poor ovarian response to gonadotrophins were studied. A series of logistic regression models were used to explore the probabilities of cancellation in relation to age and FSH. Results : Both age and basal serum FSH levels were independently associated with the risk of treatment cancellation. A low risk of treatment cancellation was observed in women under the age of 35 irrespective of serum FSH, however in older women the risk of treatment cancellation was most likely in women with a high FSH. Conclusions : In combination both age and FSH may serve as a valuable indicator of poor ovarian response leading to treatment cancellation. However, among older women FSH has particular importance, while less so in younger women with regular menstrual cycles.

Research paper thumbnail of Low-dose dexamethasone augments the ovarian response to exogenous gonadotrophins leading to a reduction in cycle cancellation rate in a standard IVF programme

Human Reproduction, 2001

BACKGROUND: Cancellation of assisted conception cycles because of poor ovarian response to gonado... more BACKGROUND: Cancellation of assisted conception cycles because of poor ovarian response to gonadotrophins is a significant problem in assisted reproduction. Various adjuvant treatments have been suggested to improve responsiveness. This study reports on the potential benefits of low dose dexamethasone. METHODS: Patients <40 years of age were invited to participate in a twin centre prospective double blind randomized placebo controlled study. A total of 290 patients were recruited and computer randomized using sealed envelopes to receive either 1 mg dexamethasone (n ϭ 145) or placebo tablets (n ⍧ 145) in addition to a standard long protocol gonadotrophinreleasing hormone analogue with gonadotrophin stimulation regime. RESULTS: A significantly lower cancellation rate for poor ovarian response was observed in the dexamethasone group compared with controls (2.8 versus 12.4% respectively, P < 0.002). Further comparisons between the dexamethasone group and controls were made of median fertilization rates (60 versus 61% respectively, NS), implantation rates (16.3 versus 11.6% respectively, NS) and pregnancy rate per cycle started (26.9 versus 17.2%, NS). The benefit was apparent in patients both with polycystic and normal ovaries. CONCLUSION: Low dose dexamethasone co-treatment reduces the incidence of poor ovarian response. It may increase clinical pregnancy rates and should be considered for inclusion in stimulation regimes to optimize ovarian response.

Research paper thumbnail of Higher cortisol:cortisone ratios in the preovulatory follicle of completely unstimulated IVF cycles indicate oocytes with increased pregnancy potential

Human Reproduction, 2002

BACKGROUND: Conception following gonadotrophin-stimulated IVF and embryo transfer has been associ... more BACKGROUND: Conception following gonadotrophin-stimulated IVF and embryo transfer has been associated with a higher intrafollicular cortisol:cortisone ratio and decreased metabolism of cortisol to cortisone. The role of glucocorticoids in human oocyte maturation is not fully understood, but active glucocorticoid (cortisol) may be important. This study relates intrafollicular cortisol and cortisone concentrations to oocyte fertilization and embryo implantation in unstimulated cycles. METHODS: Patients aged <40 years with favourable sperm underwent unstimulated IVF-embryo transfer. Study 1 related intrafollicular cortisol levels to oocyte and IVF outcome: (i) fertilized, pregnant (n ⍧ 9); (ii) fertilized, not pregnant (n ⍧ 21); and (iii) unfertilized (n ⍧ 12). Study 2 was a case-control study of 27 patients (same outcome groups of equal size) which measured intrafollicular cortisol, cortisone and the cortisol:cortisone ratio. RESULTS: Conception cycles demonstrated higher cortisol concentrations compared with the fertilized group (study 1) [median (95% confidence interval): 299 (249-330) versus 227 nmol/l (185-261); P < 0.05] and higher cortisol:cortisone ratios when compared with the unfertilized group (study 2) [7.38 (5.23-9.19) versus 3.56 (1.75-7.46) respectively; P ⍧ 0.02]. Of the women with cortisol:cortisone ratios greater than the outcome independent mean of 5.90, 58% conceived compared with only 13% with ratios Ͻ5.90 (P Ͻ 0.02). CONCLUSION: Higher cortisol:cortisone ratios in conception cycles suggest that active glucocorticoid may be important for final oocyte maturation and embryo implantation in unstimulated cycles.

Research paper thumbnail of Defining poor ovarian response during IVF cycles, in women aged <40 years, and its relationship with treatment outcome

Research paper thumbnail of Biological versus chronological ageing of oocytes, distinguishable by raised FSH levels in relation to the success of IVF treatment

Human Reproduction, 2002

BACKGROUND: The present study addresses the issue of biological ageing of the oocyte (as indicate... more BACKGROUND: The present study addresses the issue of biological ageing of the oocyte (as indicated by basal serum FSH levels) versus chronological ageing. METHODS: 1019 infertile but ovulating women were studied in their first cycle of IVF treatment. A series of logistic regression models were developed to assess statistical significance of effects of age and FSH on implantation rates and live babies born. RESULTS: The number of oocytes retrieved and embryos available for transfer declined with increasing age and basal serum FSH concentrations. Fertilizing ability of oocytes increased with advancing age but was not affected by FSH concentrations. Although the number of oocytes or embryos available for transfer had no independent effect on implantation rates, the implanting ability of fertilized oocytes (embryos) was inversely related to increasing age and independently to FSH. The chance of a baby being born, however, was determined more by age than by serum FSH. CONCLUSIONS: Ovarian ageing affecting oocyte quality and fecundity can occur independently of chronological age. This has important practical implications whereby serum basal FSH measurement may be a valuable prognostic index, though chronological age remains important.

Research paper thumbnail of Any effect of adjuvant low dose prednisolone on follicular development and embryo implantation may be masked by the concomitant use of aspirin

Research paper thumbnail of Different aetiological mechanisms for unexplained and endometriosis-associated infertility cannot be inferred from unstimulated IVF cycles using HCG to induce ovulation

Research paper thumbnail of Electronic transfer of mandatory infertility information: Survey of opinion of licensed treatment centres

Human Fertility, 2000

1. Hum Fertil (Camb). 2000;3(1):11-12. Electronic transfer of mandatory infertility information: ... more 1. Hum Fertil (Camb). 2000;3(1):11-12. Electronic transfer of mandatory infertility information: survey of opinion of licensed treatment centres. Keay SD, Corrigan E, Wardle PG, Hull MG, Jenkins JM. Centre for Reproductive Medicine ...

Research paper thumbnail of Poor ovarian response to gonadotrophin stimulation — The role of adjuvant treatments

Human Fertility, 2002

Poor ovarian response to gonadotrophin stimulation represents a clinical problem in in vitro fert... more Poor ovarian response to gonadotrophin stimulation represents a clinical problem in in vitro fertilization practice. Women showing poor ovarian response are a heterogeneous group, many of whom have a reduced ovarian reserve and consequently a lower pregnancy potential. Various management strategies have been proposed to improve ovarian response to gonadotrophins, but these have met with limited success. Adjuvant treatments aim to potentiate the effect of exogenous follicle-stimulating hormone. In separate, randomized, placebo-controlled trials low-dose dexamethasone and aspirin have been shown to reduce the incidence of poor response in an initial stimulation cycle. Preliminary studies using pyridostigmine and L-arginine in established poor responders are encouraging but require confirmation in adequately powered studies. Evidence from randomized controlled trials does not support the use of adjuvant growth hormone or growth hormone-releasing hormone in poor responders without overt growth hormone deficiency. The mechanisms of action of adjuvant treatments require further investigation.

Research paper thumbnail of Distinction between early and late ovarian hyperstimulation syndrome

Fertility and Sterility, 2000

Objective: To compare patient and cycle characteristics among three study groups: early ovarian h... more Objective: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. Design: Prospective observational study. Setting: University assisted conception service. Patient(s): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. Intervention: None. Main Outcome Measure(s): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E 2 ) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. Result(s): Women with early OHSS had significantly higher serum E 2 levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E 2 and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. Conclusion(s): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events. (Fertil Steril 2000;73:901-7.

Research paper thumbnail of Ovarian reserve and a slightly different perspective

Fertility and Sterility, 2004

Research paper thumbnail of Adjunctive use of dexamethasome in Clomid resistant patients

Fertility and Sterility, 2003