Pretreatment transvaginal ultrasound examination predicts ovarian responsiveness to gonadotrophins in in-vitro fertilization

The objective of this study was to determine the predictive value of the number of follicles seen by transvaginal ultrasound before gonadotrophin stimulation on the ovarian responsiveness of 166 infertile women undergoing in-vitro fertilization (IVF) treatment. The main variables were patient age, ovarian volume and number of ovarian follicles measuring 2-5 mm on transvaginal ultrasound before gonadotrophin stimulation. Based on the sum of ovarian follicles in both ovaries the patients were divided into three groups of inactive (<5 follicles), normal (5-15 follicles) or polycystic (PCO)-like ovaries (>15 follicles). The main outcome measure was the number of recovered oocytes. The number of follicles was correlated more strongly with the number of recovered oocytes (r2 = 0.131; P = 0.0001) than age alone (r2 = -0.053; P = 0.005). Fewer oocytes were recovered from patients with inactive ovaries (5.4 +/- 2.5; P = 0.006) than with normal (7.5 +/- 4.5) or PCO-like ovaries (10.5 +/- 5.1). Ovarian volume was correlated with the number of follicles before stimulation (P = 0.0001), but not with the number of oocytes. The number of small follicles present before ovarian stimulation was a better predictor of the outcome than ovarian volume or age alone. Patients can be identified with inactive ovaries which will have a poor response to IVF treatment, a key factor for counselling couples and optimizing resources.      

Follicular fluid concentration of leukaemia inhibitory factor is decreased among women with polycystic ovarian syndrome during assisted reproduction cycles

BACKGROUND: The possibility that a specific cytokine profile could be detected in the ovaries of patients with polycystic ovarian syndrome (PCOS) was investigated. METHOD: Enzyme-linked immunosorbent assay (ELISA) or bioassays were used to assess the concentrations of leukaemia inhibitory factor (LIF), tumour necrosis factor, interleukin 11, gamma interferon, progesterone and oestradiol in follicular fluids from preovulatory follicles collected after ovarian stimulation from 15 PCOS patients, 15 infertile control patients with regular cycles, and 8 oocyte donors. RESULTS: LIF and progesterone concentrations were significantly lower in the follicular fluid of PCOS patients (LIF median: 265 pg/ml) compared with controls (LIF median: 816 pg/ml); LIF and progesterone follicular fluid concentrations were correlated (r = 0.720, P = 0.0001). The LH/FSH ratio was negatively correlated with LIF concentrations (r = - 0.714, P = 0.0075). Although the PCOS and control patients did not differ significantly in age, ovarian reserve or IVF indication, the implantation rate was significantly lower among the women with PCOS (IR = 9 versus 21%, P = < 0.01). CONCLUSION: The specific cytokine profile of the PCOS patients is probably related to the lower implantation rate since follicular fluid LIF appears to function as an embryotrophic agent.     

Significance of ovarian histology in the management of patients presenting a premature ovarian failure

BACKGROUND: Premature ovarian failure (POF) is a heterogeneous syndrome, possibly due to mutations of genes involved in the normal development of the ovary and/or follicles. Based essentially on animal models, these mutations are associated with various ovarian phenotypes, from a complete absence of follicles to a partial follicular maturation. The aim of the present study was to determine whether ovarian histology, compared to pelvic ultrasonography, would be helpful in identifying which patients display an impaired follicular reserve and/or growth, and in orientating the search for POF aetiology. METHODS AND RESULTS: We studied a cohort of 61 patients suffering from POF with a normal karyotype. Their median age (range) at diagnosis was 26 years (15-39). The FSH plasma level was high, 67.0 IU/l (13-155). Estradiol and inhibin B plasma levels were low: 18.5 pmol/l (18.5-555) and 5 pg/ml (5-105) respectively. Both pelvic ultrasonography and ovarian biopsies were performed in each patient. The presence of follicles suggested at ultrasonography was confirmed at histology in 56% of the patients. Ovarian histology led to the distinction of two phenotypes: (i) small-sized ovaries, deprived of follicles; and (ii) normal-sized ovaries with partial follicular maturation. To confirm the value of ovarian biopsies, samples from 20 normal women were studied. These demonstrated that ovarian biopsy at random enables reliable assessment of follicular presence, especially when their size is <2 mm. CONCLUSION: Ovarian histology appears to be a reliable tool in evaluating the follicular reserve, and helpful and complementary to clinical and hormonal phenotyping in orienting the search for the various genetic causes of POF syndrome.     

Non-response to ovarian stimulation in normogonadotrophic, normogonadal women: a clinical sign of impending onset of ovarian failure pre- empting the rise in basal follicle stimulating hormone levels

The most important aspect of diminished ovarian reserve is the associated decline in reproductive potential. Assessment of ovarian reserve is mainly based on measurement of early follicular phase follicle stimulating hormone (FSH) concentration. The objective of this study was to report the identification of a group of 12 infertile women initially diagnosed as having unexplained or anovulatory infertility, who had a normal baseline hormonal profile and did not respond to repeated ovarian stimulation with gonadotrophins. All developed ovarian failure within a relatively short time span. Non-response to ovarian stimulation was defined by failure to achieve development of follicles >12 mm and failure to raise oestradiol concentration >350 pmol/l in two successive cycles of human menopausal gonadotrophin (HMG) doses of up to five ampoules per day for 5-8 days. Within a mean of 9 months following the failed attempts of ovarian stimulation the mean day 3 FSH concentrations rose from 5.4 +/- 2.7 IU/l to 53.5 +/- 19.7 IU/l. In these patients, day 3 FSH concentration failed to indicate the low ovarian reserve manifested only by lack of clinical response to treatment with gonadotrophins which was the first sign of impending ovarian failure. We conclude that women with normal early follicular phase serum FSH concentrations who do not respond to ovarian stimulation by HMG are at risk of developing ovarian failure within several months.      

Measurement of ovarian volume by transvaginal sonography before ovulation induction with human menopausal gonadotrophin for in-vitro fertilization can predict poor response

The study tests the hypothesis that small ovaries measured on transvaginal sonography (TVS) are associated with a poor response to ovulation induction by human menopausal gonadotrophin (HMG) for in- vitro fertilization (IVF). A total of 140 infertile patients with morphologically normal ovaries undergoing IVF was studied. The mean ovarian volume of each patient was measured on TVS before starting HMG. Subsequent routine IVF management was conducted without knowledge of the results of TVS. The mean ovarian volume was 6.3 cm3 (range 0.5- 18.9, SD= 3.1). Patients (n = 17; group A) with small ovaries of < 3 cm3 (i.e. overall mean volume - 1 SD) were compared to patients (n = 123; group B) with ovaries > or = 3 cm3. Both groups were of similar age (mean 35.8 versus 34.4 years). Early basal FSH concentrations were increased in group A (9.5 versus 7.0 mIU/ml, P = 0.025). The cycle was abandoned before planned oocyte recovery in nine patients (52.8%) from group A and in 11 patients (8.9%) from group B because of poor response to ovulation induction (P < 0.001). Increased age and ovarian volume were associated independently with cancellation of the cycles. The remaining eight patients from group A who had oocytes retrieved required higher doses of HMG (87.5 versus 53.8 ampoules, P < 0.01), yielded fewer follicles (10.3 versus 14.5, P < 0.05) and fewer oocytes were recovered from them (6.8 versus 11.0, P < 0.05) compared with group B. There was no difference in the fertilization or pregnancy rates or the number of embryos available for transfer in either group. Our results indicate a strong association between ovarian volume and ovarian reserve. Small ovaries are associated with poor response to HMG and a very high cancellation rate during IVF. Assessment of ovarian size should be an integral part of infertility evaluation.      

Young age does not protect against the adverse effects of reduced ovarian reserve--an eight year study

BACKGROUND: Ovarian reserve significantly influences IVF outcome. Low response to ovarian stimulation due to reduction of ovarian reserve is occasionally encountered in young women. The aim of this study was to evaluate the outcome of IVF treatment in young patients with reduced ovarian reserve. METHODS AND RESULTS: Between January 1993-2001, 762 consecutive patients satisfied the definition of reduced ovarian reserve (raised early follicular phase FSH or gonadotrophin stimulation cycles where three or fewer oocytes were retrieved after routine FSH stimulation) and were included in the study. They were classified into three age groups: young (< or = 30 years), intermediate (31-38 years) and older (>38 years). The three age groups were similar with respect to basal (day 3) serum FSH and estradiol concentrations, cause of infertility and number of previous treatment cycles. Implantation (13, 9.6 and 9.8%), clinical pregnancy (11.8, 10.2 and 10%) and live birth (7.4, 7.3 and 6.8%) rates were not significantly different in the three age groups respectively (P > 0.05). CONCLUSION: This study shows that younger patients with reduced ovarian reserve have a poor outcome of IVF treatment similar to their older counterparts. Such information may be helpful in counselling these patients who otherwise might anticipate an outcome related to their chronological age.     

Leukaemia inhibitory factor expression in human follicular fluid and ovarian cells

Leukaemia inhibitory factor (LIF) is a 43 kDa glycoprotein with a remarkable range of biological actions in different tissue systems. LIF improves the rate of fertilization of mouse oocytes in vitro and up- regulates aromatase enzyme. We postulated that LIF may be an important modulator of ovarian function and may also improve embryo quality in humans. Follicular fluid samples from patients undergoing in-vitro fertilization (IVF) and embryo transfer (n = 123), from women undergoing ovarian stimulation (n = 4) and from women undergoing laparoscopy for tubal ligation during their follicular phase (n = 3) were used. Follicular fluid LIF, oestradiol, and progesterone were measured and embryo quality was assessed. Granulosa-lutein cells were cultured for 3 days in Ham's F-12:Dulbecco's modified Eagle's medium (DMEM). Ovarian stromal cells, isolated by enzymatic dispersion of ovarian tissue, were also cultured in the same medium. Following experimental treatments, LIF mRNA and protein concentrations were quantified. The concentration of LIF was 0.8 +/- 0.3 (mean +/- SEM) pg/ml in pre-human chorionic gonadotrophin (HCG) follicular fluid samples and 13.0 +/- 1.1 pg/ml in post-HCG follicular fluid samples (P < 0.05). LIF levels were undetectable in three follicular fluid samples obtained during unstimulated follicular phase. There was a correlation between follicular fluid LIF and follicular fluid oestradiol concentrations (r = 0.36; P = 0.0001) and the number of grade I embryos (r = 0.62; P = 0.01). LIF mRNA and the protein were expressed constitutively but in low amounts in the ovarian stromal cell cultures. The concentrations of LIF mRNA as well as protein were increased by interleukin (IL)-1alpha and tumour necrosis factor alpha (TNF alpha) in a time- and concentration-dependent manner. Purified granulosa-lutein cells expressed low amounts of LIF mRNA and protein which were not significantly increased by IL-1alpha or TNF alpha. Our findings suggest that HCG stimulates the expression of LIF in follicular fluid. Both granulosa-lutein and ovarian stromal cells express the LIF mRNA and produce the protein. Modulation of LIF in these cells may play an important role in the physiology of ovulation and early embryo development.      

Follicle stimulating hormone measured in unextracted urine throughout the menstrual cycle correlates with age and ovarian reserve

BACKGROUND: A method was previously described to measure FSH reliably in unextracted urine. The aim of the current study was to establish the course of FSH measured in urine throughout the cycle. METHOD: Daily urinary FSH (uFSH) concentrations were determined in 14 regularly menstruating volunteers aged 23-39 years during one complete menstrual cycle. RESULTS: In each subject, mean daily uFSH measured in urine, as gold standard for FSH tone, correlated significantly with FSH in early follicular phase fixed to menstruation on cycle day 3 (r = 0.75, P = 0.002), or fixed to ovulation 9 days before the pre-ovulatory FSH surge (r = 0.87, P = 0.0001), or when selected as being the highest follicular phase value (r = 0.91, P = 0.0001). Age correlated significantly with mean daily uFSH (r = 0.67, P = 0.009), highest follicular phase uFSH (r = 0.60, P = 0.024), uFSH on cycle day 3 (r = 0.80, P = 0.0006), and uFSH 9 days before FSH surge (r = 0.65, P = 0.0016). The uFSH was also measured on cycle day 3 in 104 IVF patients in a cycle prior to pituitary down-regulation. The uFSH correlated significantly with numbers of follicles (P = 0.02) and oocytes (P = 0.024). CONCLUSION: It is concluded that cycle day 3 uFSH is a good reflection of the mean uFSH of the complete cycle, and there is a highly significant correlation between uFSH and age and ovarian reserve. Measurement of FSH in urine on cycle day 3 seems to be a reliable and non-invasive tool for determining ovarian reserve in IVF.     

Ovarian reserve and reproductive age may be determined from measurement of ovarian volume by transvaginal sonography

BACKGROUND: The human ovary contains a fixed number of primordial follicles that decreases bi-exponentially with age, culminating in the menopause at an average age of 50-51 years. There currently is no reliable test of ovarian reserve for individual women that will accurately predict their remaining reproductive lifespan. METHODS AND RESULTS: We use the Faddy-Gosden model of human primordial follicle population decline to describe the natural decay of the ovarian follicle pool. Assuming that the wide distribution for age at menopause is due to the wide variation in number of primordial follicles at birth, we describe follicle population decline for early and late menopausal women. Using published data on age-related ovarian volume as measured by transvaginal sonography, we have obtained a highly significant correlation between primordial follicle population and ovarian volume. We show that ovarian volume in women aged 25-51 years accurately reflects the number of primordial follicles remaining, and describe how measurement of ovarian volume by transvaginal sonography may determine ovarian reserve and reproductive age. CONCLUSIONS: The accurate assessment of ovarian reserve will revolutionize the management of women requesting assisted conception, those who have had treatment for childhood cancer and those who are considering delaying a family for personal or professional reasons.     

Timing of FSH administration for ovarian stimulation in normo-ovulatory women: comparison of an early or a mid follicular phase initiation of a short-term treatment

BACKGROUND: In normo-ovulatory infertile women undergoing mild ovarian stimulation out of IVF, FSH stimulation regimen must be carefully adjusted to control the number of recruited follicles and to prevent multiple pregnancies. The aim of this prospective study was to assess the effect of the timing of FSH administration (fixed dose and duration) on the number of large follicles. METHODS: Women were prospectively randomized by means of sealed envelopes to receive daily 112.5 IU recombinant FSH (rFSH), either from cycle day (CD) 2-6 (Group A) or from CD 7-11 (Group B). Hormonal measurements and follicular ultrasound assessments were performed on CD 2, 7 and 12. RESULTS: On CD 12, the development rate of exactly two follicles >or=14 mm in diameter was significantly lower in Group A than in Group B (4% of women versus 42%, P = 0.002). Although the pattern of serum estradiol (E(2)) concentrations in Group A displayed a plateau from CD 7, the cancellation rate for overstimulation (more than three follicles >or=14 mm in diameter) was significantly increased (P = 0.009). CONCLUSIONS: Preventing the closure of the FSH window by mid to late follicular phase FSH administration better fulfils the objective of obtaining a limited number of large follicles than surpassing the FSH threshold by an early administration.     

Effect of age on ovarian stromal flow measured by three-dimensional ultrasound with power Doppler in Chinese women with proven fertility

BACKGROUND: Increasing age is associated with reduced ovarian stromal blood flow detected by three-dimensional (3D) power Doppler ultrasound in infertile patients. However, little information exists in the literature regarding the effect of age on the ovarian stromal blood flow in fertile women. METHODS: On the second to fourth day of their menstrual cycle, fertile Chinese women who had regular monthly cycles and no history of tubal and ovarian surgery underwent a transvaginal scan with 3D power Doppler to determine total antral follicle count (AFC), total ovarian volume, total ovarian vascularization index (VI)/flow index (FI)/vascularization flow index (VFI). Serum FSH and vascular endothelial growth factor concentrations were checked. RESULTS: Out of 177 women scanned, 138 women were included in the final analysis. Total AFC and serum FSH were significantly different among four age groups (< or = 30, 31-35, 36-40 and > or = 41 years). Total ovarian VI and VFI were significantly lower in women aged > or = 41 years. AFC had the best correlation with the age of women, followed by serum FSH concentration and ovarian 3D power Doppler indices. The rate of decline of total ovarian VI was 0.18% per year. CONCLUSION: Ovarian stromal blood flow was significantly reduced only in women aged > or = 41 years.     

Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries

BACKGROUND: At the time of cryopreservation of ovarian tissue for fertility preservation a small biopsy of ovarian cortex is usually taken for histological evaluation of the follicular reserve. The purpose of this study was to evaluate the distribution and density of primordial follicles in single pieces of cortex from individual patients and in pieces of cortex comprising entire ovaries, all prepared for cryopreservation. METHODS: Cortical biopsies from 21 patients and the whole cortex of one ovary were evaluated histologically prior to cryopreservation. In addition, the cortex of two whole ovaries was cryopreserved before histological evaluation. The volume of each cortical fragment was measured, all follicles counted and the follicular density calculated. RESULTS: In individual pieces of cortex follicular density showed a significant inverse linear correlation with age. The follicular density per cortical fragment prepared from each of the three entire ovaries varied from 1.8 to 166, 0.007 to 140 and 0.04 to 4.48 follicles/mm(3) cortical tissue. CONCLUSION: The density of primordial follicles varied more than two orders of magnitude in cortical fragments from each of the three ovaries. Primordial follicles were very unevenly distributed throughout the cortex of these ovaries, although a significant linear correlation between age and follicular density was found.     

Insulin-like growth factor binding protein-1 and ovarian stimulation.

Serum concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) were measured in 42 patients with tubal infertility undergoing two different regimens of ovarian stimulation for in-vitro fertilization. The first group comprised 24 women given a luteinizing hormone-releasing hormone agonist analogue (buserelin, LHRHa) on cycle days 1-4 followed by follicle-stimulating hormone and human menopausal gonadotrophin (LHRHa group). The second group of 18 women received clomiphene citrate and gonadotrophins (CC group). On the day of human chorionic gonadotrophin administration, the sum of follicular diameters (P less than 0.05) and the number of follicles punctured in the LHRHa group (P less than 0.01) were significantly higher than in the CC group. In spite of the greater number of follicles, the oestrogen levels were similar in both groups, but women in the LHRHa group had significantly higher serum IGFBP-1 concentrations during the last 5 days of stimulation. These results suggest that the stimulated preovulatory follicles may contribute to the elevation of serum IGFBP-1.     

Evidence for different aetiologies of low estradiol response to FSH: age-related accelerated luteinization of follicles or presence of ovarian autoantibodies

BACKGROUND: We found granulosa cells of low responders (LR) expressed more LH receptors, suggesting that follicles were more luteinized than normal responders (NR). The objectives were to test the hypothesis that follicles of LR were more luteinized than follicles of NR, and to determine if LR with (LR+) and without (LR-) ovarian antibodies differed. METHODS: Hormone levels and ovarian autoantibodies (OVAB) were measured in follicular fluid from mature follicles (>17 mm), and in serum obtained on the day of oocyte retrieval during controlled ovarian stimulation. The gonadotrophin response was defined as a ratio of peak estradiol/number of FSH ampoules. RESULTS: NR (32.5 +/- 4.6 years; n = 11) were similar in age to LR+ (33.4 +/- 4.2 years; n = 9) and were younger than LR- (37.1 +/- 3.8 years; n = 12) (P = 0.03). Likewise, dehydroepiandrosterone sulphate was lower in LR- compared with LR+ or NR (P < 0.01). FSH, progesterone, inhibin-A and vascular endothelial growth factor levels were higher in follicular fluid of LR than NR. LR- and LR+ differed. For example, the follicular fluid progesterone/estradiol ratio was similar in NR (11.1 +/- 8.9) and LR+ (9.8 +/- 6.6) but was lower than LR- (22.9 +/- 19.6) (P = 0.05). Serum hormone levels did not reflect follicular fluid hormone profiles. CONCLUSIONS: In the absence of ovarian antibodies, low responses are associated with higher age and accelerated luteinization of mature follicles, rather than diminished responsiveness. Ovarian antibody may be an additional tool to predict and individualize treatment regimens in poor responders.     

Relationship of ovarian stimulation response with vascular endothelial growth factor and degree of granulosa cell apoptosis

BACKGROUND: The aim of this study was to evaluate the concentration of vascular endothelial growth factor (VEGF) in follicular fluid and in granulosa cell cultures in relation to the degree of apoptosis in granulosa cells from patients with different types of ovarian response to controlled ovarian hyperstimulation. METHODS: We studied 30 women who underwent controlled ovarian hyperstimulation and oocyte retrieval. Group A comprised patients with 1-4 follicles (n = 10), group B patients with 5-14 follicles (n = 10) and group C patients with >15 follicles (n = 10). RESULTS: Mean (+/-SD) VEGF concentrations in follicular fluid were 1232 +/- 209, 813 +/- 198 and 396 +/- 103 pg/ml for groups A, B and C respectively (P > 0.01). Concentrations of VEGF in granulosa cell supernatant were 684 +/- 316, 1101 +/- 295 and 1596 +/- 227 pg/ml respectively (P < 0.05). Percentages of apoptotic cells in granulosa cells culture was 55.02 +/- 7.5, 23.98 +/- 4.4 and 14.2 +/- 2.3% respectively (A versus B, P < 0.01, A versus C, P < 0.006, B versus C, NS). CONCLUSIONS: Our findings showed that in patients with decreased ovarian response to controlled ovarian hyperstimulation, follicular fluid VEGF concentration is elevated, the concentration from granulosa cells culture supernatant is decreased and the percentage of apoptotic granulosa cells is increased, while opposite findings occurred in patients with normal or hyper-responses.     

Assessment of ovarian reserve. Ovarian biopsy is not a valid method for the prediction of ovarian reserve

The evaluation of ovarian reserve, often critical for the elderly infertile woman, is notoriously difficult and inaccurate. The place of ovarian biopsy in this evaluation has been hotly disputed for three decades, but not resolved. To examine the feasibility of ovarian biopsy for this purpose, a project was designed to estimate the total number of oocytes in a human ovary and investigate whether any biopsy regimen is representative of the follicular reserve in an individual. Ovaries removed from patients of reproductive age during operations not involving ovarian pathology were utilized to count the number and type of follicles found in multiple biopsies of 2 and 5 mm and in the whole ovary. Representative results taking into account the total number of follicles found in the whole ovary showed that predicted values based on the biopsies were extremely varied. We concluded that due to the huge variation in the distribution of follicles across the surface of the ovary, there is no place for this procedure in clinical evaluation of reproductive ageing in the individual patient.     

Accuracy of ovarian reserve tests.

Several tests predict ovarian reserve in women undergoing assisted reproductive technologies. However, the accuracy of these tests in assessing the number of the remaining follicles within the ovary (ovarian reserve) has not been previously validated. The aim of this study was to assess the accuracy of ovarian reserve tests, namely basal and clomiphene-stimulated follicle stimulating hormone (FSH) concentrations and gonadotrophin-releasing hormone (GnRH) agonist stimulation test in predicting the number of the follicles within the ovaries. The ovaries of 22 parous women over 35 years of age who underwent oophorectomy were examined histologically for follicle number. Early follicular phase serum FSH, clomiphene citrate challenge tests (CCCT) and GnRH agonist stimulation test (GAST) were performed in the menstrual cycle prior to the surgery. The predictive value of these tests was then assessed. A positive correlation was detected between basal serum oestradiol concentrations and follicles per unit tissue but no significant correlation was detected between basal and clomiphene-stimulated FSH and follicles per unit tissue. The receiver operator characteristic curves indicated that the clomiphene citrate challenge test was the most accurate of the three tests assessed. In conclusion, none of the tests in this study accurately reflects ovarian reserve.     

The effects of 'coasting' on follicular fluid concentrations of vascular endothelial growth factor in women at risk of developing ovarian hyperstimulation syndrome

BACKGROUND: The aim of this study was to assess the effect of withholding gonadotrophins (coasting) during controlled ovarian stimulation (COS) on individual follicle concentrations of follicular fluid vascular endothelial growth factor (VEGF) in women at high risk of developing ovarian hyperstimulation syndrome (OHSS). METHODS: Twenty-two women who had been coasted and 26 optimally responding women (control group) undergoing COS for IVF were studied. At the time of oocyte retrieval, the follicular fluid from four to six individual follicles of different sizes was collected for VEGF analysis. RESULTS: A total of 118 follicles was analysed in the coasted group and 137 in the control group. A negative correlation was observed between the follicle size and VEGF concentration (r = -0.18, P = 0.03) in the control group, which was not seen in the coasted group. Similarly, the correlation between oestradiol (E(2)) and VEGF (r = 0.4, P < 0.0001) observed in the control group was not apparent in the coasted group. Significantly lower concentrations of VEGF were seen in the follicular fluid of the coasted patients. CONCLUSIONS: It is clear that there are differences in follicular fluid VEGF concentrations between the two groups. It is possible that coasting alters the capacity of the granulosa cells to produce VEGF and/or their response to hCG and in this way acts to reduce the severity and incidence of severe OHSS.     

Total ovarian volume before human chorionic gonadotrophin administration for ovulation induction may predict the hyperstimulation syndrome

Total ovarian volumes were measured before the administrationof HCG in 42 women undergoing treatment for infertility by in-vitrofertilization (IVF) and embryo transfer and considered to havean exaggerated response to stimulation (>20 follicles). Sevenwomen who subsequently developed moderate or severe ovarianhyperstimulation syndrome (OHSS) (n = 7; group 1) were comparedwith 35 matched controls (five matched controls per case; n= 35; group 2) of similar age, number of follicles and durationof infertility who underwent follicular stimulation, oocyterecovery, in-vitro fertilization and embryo transfer duringthe same period but did not develop moderate or severe OHSS.The mean age, duration of infertility and total number of follicleswere similar but the mean total ovarian volume was significantlyhigher in the group of women who developed moderate or severeOHSS compared with controls (271.00 ± 87.00 versus 157.30± 54.20 ml; P < 0.01). We conclude that total ovarianvolume measured before HCG administration is higher in womenwho develop moderate or severe OHSS compared with controls andmay therefore be used as an additional parameter in the preventativestrategy for the ovarian hyperstimulation syndrome.     

The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age

BACKGROUND: The purpose of this study was to compare the predictive capacity of several markers of reproductive age in normal women. METHODS: Healthy female volunteers (n = 162) aged 25-46 years with proven, normal fertility and regular menstrual cycles were recruited. In this selected group, chronological age was assumed to approximate reproductive age and, therefore, was taken as the proxy-variable for reproductive age. The number of antral follicles with 2-10 mm diameter, total ovarian volume, total follicular volume, mean follicular volume, and volume of either the smallest or largest ovary were estimated by transvaginal sonography of the ovaries. Serum levels of early follicular FSH, estradiol and inhibin B, as well as the response of estradiol and inhibin B to exogenous GnRH agonist administration (GAST), were also evaluated. RESULTS: Regression analysis revealed that the antral follicle number showed the highest correlation with age (r = -0.68, P = 0.001), and explained 46% of its variance. All other variables, except inhibin B, were moderately correlated with age. Responses of estradiol and inhibin B to the GnRH agonist were moderately correlated with age, but highly correlated with the number of antral follicles. CONCLUSIONS: It is concluded that the number of antral follicles has the closest association with chronological age in normal women with proven fertility. As stimulated estradiol and inhibin B clearly reflect the size of the antral follicle cohort, the GAST may be considered the second best single test to predict reproductive age.