Clinical and laboratory evaluation of hospitalized patients with severe ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is an important complication of ovarian stimulation and IVF that enhances patients' morbidity. To evaluate any increased incidence of hospitalization from severe OHSS during 2000, this study analysed certain clinical, ultrasound and laboratory characteristics of hospitalized patients with severe OHSS. These studies were carried out on women undergoing IVF who were hospitalized because of severe OHSS between 1996 and 2000 at the H?pital Antoine Béclère. Patients' ages and serum hormone concentrations were collected on day 3 of ovarian stimulation for various assays, and laboratory and ultrasound measurements taken during ovarian stimulation for IVF were compared. An increase was noted during last year in the frequency of the severe form of OHSS requiring hospitalization (0.9 versus 1.8%, P < 0.05). Patients' ages and hormonal characteristics on day 3 of menstrual cycle, and laboratory and ultrasound variables were similar between the two groups. In addition, the increased incidence of OHSS during 2000 was not associated with any special laboratory or ultrasound parameter, and the policy of ovarian induction had not changed. It is essential to introduce a simple ovarian stimulation protocol providing acceptable IVF results with a minimum of risk.     

Role of three-dimensional ultrasonographic measurement of endometrium volume as a predictor of pregnancy outcome in an IVF-ET program: a preliminary study

OBJECTIVE: To evaluate the role of three-dimensional (3D) ultrasonographic measurement of the endometrium in predicting pregnancy in an IVF-ET program. DESIGN: Prospective study. SETTING: Center for assisted reproductive techniques. PATIENT(S): 65 women undergoing controlled ovarian hyperstimulation for IVF. INTERVENTION(S): Ultrasonographic examination on the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial volume, endometrial thickness, and pregnancy rate. RESULT(S): The mean (+/-SD) endometrium volume (4.16 +/- 1.97 mL), endometrium thickness (11 +/- 2 mm), and estradiol level (1686.82 +/- 1057.10 pg/mL) in 21 pregnant women on the day of hCG administration did not differ statistically differ from the respective values in 44 nonpregnant women (4.53 +/- 1.79 mL; 11 +/- 2 mm, 1883.56 +/- 1147.21 pg/mL). Receiver-operating characteristic curves showed that the area under curve (AUC) was 0.57 for endometrial volume and 0.48 for endometrial thickness. Using a cut-off value of 2.5 mL for endometrial volume to predict pregnancy, results of the Fisher exact test were statistically significant. No significant cut-off value was found for endometrial thickness. CONCLUSION(S): Endometrial volume and thickness on the day of hCG administration did not predict occurrence of pregnancy. A minimum volume of 2.5 mL appeared to favor pregnancy. The predictive value of 3D ultrasonographic measurement of endometrial volume and thickness was better than that of 2D measurement.     

Comparison of Basal and Clomiphene Citrate Induced FSH and Inhibin B, Ovarian Volume and Antral Follicle Counts as Ovarian Reserve Tests and Predictors of Poor Ovarian Response in IVF

PURPOSE: To compare basal and clomiphene citrate (CC) induced follicle-stimulating hormone (FSH), estradiol (E2), and inhibin B levels with ultrasound indices of ovarian reserve in infertile women and to test the prognostic value of these tests on response to ovarian stimulation in in vitro fertilization (IVF). METHODS: Fifty-six patients had basal and CC induced serum hormone levels and ultrasound measured mean ovarian volume (MOV) and mean antral follicle counts (MFC). Thirty-two patients were then appropriately selected to have a total of 41 cycles of IVF/ICSI treatment. RESULTS: Women with diminished ovarian reserve had lower MOV, MFC, day 3 and day 10 inhibin B levels (p < 0.001). Only basal and CC induced FSH and inhibin B correlated with MOV and MFC. Poor responders in IVF/ICSI had higher basal FSH (p < 0.05), lower basal and induced inhibin B levels (p < 0.05), and lower MOV and MFC (p < 0.01) than normal responders. Ovarian volume alone was better than age and basal hormones in predicting poor ovarian response, while abnormal CC test was the only independent significant factor in predicting ovarian response. However, age was the only independent predictor of pregnancy in IVF as compared to hormonal and ultrasound indices of ovarian reserve. CONCLUSION: CC test and ovarian volume are better than other hormonal and sonographic tests in predicting the response to ovarian stimulation in IVF cycles.     

Placental protein 14 concentrations in circulation related to hormonal parameters and reproductive outcome in women undergoing IVF/ICSI

Serum concentrations of placental protein 14 (PP14), steroids and gonadotrophins were related to the outcome of IVF/intracytoplasmic sperm injection in 195 normogonadotrophic women subjected to the long protocol gonadotrophin-releasing hormone agonist (GnRHa; buserelin) pituitary down-regulation protocol and gonadotrophin stimulation (HMG or rFSH). Pituitary down-regulation was initiated on cycle day 21 and the patients were randomized to either intranasal or s.c. administration of buserelin. After 14 days of down-regulation, the patients were randomized on stimulation day 1 (S1) to ovarian stimulation with 225 IU per day of either human menopausal gonadotrophin (HMG) or recombinant FSH (rFSH) for a fixed period of 7 days. The daily gonadotrophin dose was adjusted on the following day according to ovarian response. Patient's blood was sampled for PP14 and hormone analysis on cycle days 21, S1, S8 and on the day of oocyte retrieval. Mean concentrations of PP14 on day 21 of the cycle were significantly lower in conception than in non-conception cycles, whereas progesterone and oestradiol were similar in conception and non-conception cycles. PP14 concentrations on the first day of stimulation and at oocyte retrieval were significantly higher in conception than in non-conception cycles, whereas concentrations after 8 days of stimulation were similar. Neither mode of GnRHa administration nor type of gonadotrophin significantly influenced PP14 concentrations throughout ovarian stimulation. Circulating PP14 is thus an important physiological signal of the fertility status of the individual in the cycle antecedent to and during ovarian stimulation. Measuring mid-luteal serum PP14 may offer a clinical test helping to decide if infertility treatment should be initiated in the subsequent cycle.     

Value of the serum estradiol level for preventing ovarian hyperstimulation syndrome: a retrospective case control study

OBJECTIVE: To assess the value of different serum E(2) cut-off levels for predicting women at risk for ovarian hyperstimulation syndrome (OHSS). DESIGN: Retrospective case-control study of a cohort of women undergoing assisted reproduction treatment (ART) over 12 months. SETTING: Tertiary university hospital. PATIENT(S): The study group included women with OHSS who fulfilled the endocrine inclusion criteria (n = 40). The control group was a random sample (n = 40) from the cohort of women undergoing ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): To evaluate the sensitivity and specificity of different serum E(2) cut-off levels on day 11 of ovarian stimulation in preventing the establishment of OHSS. RESULT(S): Three hundred ninety-nine cycles (IVF and intracytoplasmic sperm injection) were undertaken between June 2000 and May 2001. The study group (n = 40) was compared with the control group (n = 40) undergoing ART during the same period of time. On day 8 of ovarian stimulation, the mean (SD) E(2) level in the study group was 8,517(5.3) pmol/L (2,320 pg/mL), and in the control group it was 2,540 (2.6) pmol/L (691 pg/mL). On day 11 of stimulation the mean (SD) E(2) level was 15,662 (4.2) pmol/L (4,266 pg/mL) and 5,804 (4.5) pmol/L (1,581 pg/mL), respectively. Twenty-four (60%) women who developed OHSS had E(2)levels >6,000 pmol/L (1,634 pg/mL) on day 8 and above 11,000 pmol/L (2,996 pg/mL) on day 11. Sixteen (40%) had E(2) levels <6,000 pmol/L (1,634 pg/mL) on day 8, but all had levels above 11,000 pmol/l (2,996 pg/mL) on day 11. CONCLUSION(S): A serum E(2) level of 12,315 pmol/L (3,354 pg/mL) on day 11 of ovarian stimulation gives a sensitivity and specificity of 85% for the detection of women at risk for OHSS.     

Results of in vitro fertilization cycles in women aged 43-45 years.

Our objective was to evaluate the results of in vitro fertilization (IVF) cycles in the elderly (43-45 years old) female population. All consecutive women aged 43-45 years admitted to our IVF unit from January 1996 to December 2001 were enrolled in the study. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred and pregnancy rate were assessed. Seven hundred and eight consecutive IVF cycles in 276 patients were evaluated. Two hundred and seven cycles were cancelled (cancellation rate 29.2%). Forty-seven patients achieved a clinical pregnancy (pregnancy rate 6.6% per cycle and 9.4% embryo transfer) with a 30% live birth rate. In patients who underwent embryo transfer, there were no differences between conception and non-conception cycles in patient's age, number of gonadotropin ampules used, length of ovarian stimulation, number of oocytes retrieved, fertilization rate or cleavage rate. However, the conception cycles were associated with a significantly lower peak estradiol level (p < 0.04) and higher number of total (p < 0.03) and good-quality (p < 0.005) embryos transferred, in addition to a lower ratio of estradiol level/number of follicles > 14 mm on day of human chorionic gonadotropin administration and of estradiol level/number of oocytes retrieved. We conclude that, although older female age is a major contributor to IVF failure, successful IVF cycles can be expected in patients aged 43-45 years in the presence of low ratios of peak estradiol to either number of follicles > 14 mm on day of human chorionic gonadotropin administration or number of oocytes retrieved that reach the stage of embryo transfer with at least two good-quality embryos.     

Use of follicle-stimulating hormone test to predict poor response in in vitro fertilization

OBJECTIVE: Optimized ovarian stimulation protocols are required for the success of in vitro fertilization (IVF). The purpose of this study was to estimate whether the ovarian reserve test using exogenous follicle-stimulating hormone (FSH) could predict ovarian response in IVF. METHODS: This was a prospective observational study of 110 patients who underwent their first IVF cycle. The FSH test was administered as 150 IU of urinary FSH daily from day 3 to day 6 of the menstrual cycle preceding the IVF cycle for evaluation of the plasma estradiol level. Outcomes of IVF, including ovarian response, were analyzed. RESULTS: A negative correlation was observed between the duration of stimulation and the result of the FSH test (r = -.238, P = .014) and between the dose of FSH per retrieved mature oocyte (metaphase II oocyte) and the result of the FSH test (r = -.308, P < .001). In addition, our results showed that the result of the FSH test was significantly lower in poor responders defined by FSH of 400 IU/metaphase II oocyte or greater (207 +/- 149 compared with 293 +/- 174 pg/mL, P = .007). CONCLUSION: The FSH test can be a useful tool for determining the conditions of individualized clinical management plans and optimizing stimulation protocols in IVF.     

Ovarian stimulation and intrauterine insemination in women aged 40 years or more

Fertility decreases with advancing age. This study retrospectively reviewed the results of ovarian stimulation and intrauterine insemination (IUI) in women 40 years old with diminished ovarian reserve or unexplained infertility who underwent treatment with ovarian stimulation/IUI with clomiphene citrate or gonadotrophin and compared them with the results of IVF and in-vitro maturation (IVM) treatments. The main outcome measures were pregnancy and live-birth rates. The profiles of the patients in ovarian stimulation, IVM and IVF groups were comparable. There were no clinical pregnancies in the clomiphene citrate and IVM groups. The clinical-pregnancy rates in the gonadotrophin and IVF groups were 2.6% and 16.9% and the live-birth rates were 2.6% and 13.7%, respectively. Compared with ovarian stimulation, IVF is most effective for women aged 40 years or more. Attempting success with ovarian stimulation or IVM will delay conception unnecessarily.     

Ovarian stromal vascularity is not predictive of ovarian response and pregnancy

The role of ovarian stromal vascularity in the prediction of the ovarian response and pregnancy in infertile women was evaluated by comparing age of women, body mass index (BMI), basal FSH concentration, antral follicle count (AFC) and ovarian stromal vascularity indices measured by three-dimensional power Doppler ultrasound. A total of 111 women in their first IVF cycle were analysed. They were aged <40 years with basal FSH concentration <10 IU/l on recruitment for IVF treatment. AFC, mean ovarian volume and mean ovarian 3D power Doppler flow indices were determined on day 2 of the treatment cycle prior to a standard regimen of ovarian stimulation. Ovarian response was represented by the number of oocytes, serum oestradiol, the duration and dosage of gonadotrophins. AFC achieved the best predictive value in relation to the number of oocytes obtained, followed by age of women and BMI. Basal FSH concentration was the only predictive factor for the duration and dosage of gonadotrophin used. Mean ovarian 3D power Doppler flow indices were not predictive of pregnancy in a multiple logistic regression analysis. Ovarian 3D power Doppler flow indices measured after pituitary down-regulation were not predictive of the ovarian response and pregnancy in the IVF treatment.     

Converting an IVF cycle to IUI in low responders with at least 2 follicles

OBJECTIVE: To assess the utility of transforming an in vitro fertilization (IVF) cycle with low ovarian response to an intrauterine insemination (IUI) cycle. STUDY DESIGN: The inclusion criteria were women undergoing IVF because of idiopathic infertility, a mild to moderate male factor or IUI failure, with at least 1 normal, patent tube. When ovarian stimulation produced 2-4 follicles > or = 18 mm, the IVF cycle was converted to an IUI cycle. In cases with 4 follicles, estradiol had to be < 800 pg/mL. A total of 57 cycles were analyzed. RESULTS: The clinical pregnancy rate (PR) was 14.0% (8/57) in IVF cycles converted to IUI vs. 17.3% in our general IUI population (240/1,389). Converted cycles were associated with longer ovarian stimulation and with lower estradiol levels and less mature follicles than was IUI in the general population. There was a trend toward higher PR in women starting ovarian stimulation with 225 IU of gonadotropins (18.2%) than in those starting with higher doses (8.6%) (P > .05). CONCLUSION: In IVF low responders with at least 1 normal, patent tube when 2-4 follicles are observed, converting the IVF cycle to an IUI cycle yields a PR of 14.0%. This option should be considered in the management of low responders, especially those not stimulated with high doses of gonadotropins.     

Outcome of in vitro fertilization in patients with proven poor ovarian responsiveness after early vs. mid-follicular LH exposure: a prospective, randomized, controlled study

Objective

To compare early vs. mid-follicular exposure to LH in patients with poor ovarian responsiveness undergoing in vitro fertilization (IVF).

Design

Prospective, randomized, controlled trial.

Setting

University Hospital, University-affiliated private Clinic.

Patients

Five hundred-thirty women with poor ovarian responsiveness during the first IVF cycle, undergoing their second IVF attempt.

Interventions

In a GnRH-analogue long protocol, ovarian stimulation with recombinant FSH (300 IU/day) plus randomly assigned addition of recombinant LH (150 IU/day) from day 1 (early LH exposure; n = 264) or from day 7 (late LH exposure; n = 266).

Main outcome measure(s)

Primary outcome was the number of oocytes retrieved. Secondary outcomes were: cancellation rate, total gonadotropin dose, duration of ovarian stimulation, number of embryos available for transfer, pregnancy rate per started cycle, per OPU and per embryo transfer, implantation rate, delivered/ongoing pregnancy rate.

Results

Apart from the totally administered LH dose, that was significantly higher in the group receiving it from day 1, all parameters related to IVF outcome were non significantly different in the two groups.

Conclusions

Adding LH to FSH from day 1 or from day 7 of ovarian stimulation in a GnRH-agonist long protocol exerts comparable effects on IVF outcome in poor responders.     

Prediction of pregnancy in IVF cycles on the fourth day of ovarian stimulation

Purpose Prediction of IVF outcome on the first days of ovarian stimulation has focused clinical research for many years. The aim of this work is to predict the probability of pregnancy on the fourth day of ovarian stimulation for IVF cycle, using parameters usually determined in this stage—estradiol, antral follicle count—together with parameters determined previously: FSH on the third day of cycle and women age. Materials and methods One hundred and ten patients with primary infertility due to a tubal factor were recruited to participate in a prospective study. FSH was determined on the third day of spontaneous cycle. Antral follicles and estradiol were measured on the fourth day of ovarian stimulation. After oocyte pick-up, quality and quantity of oocytes and embryos and pregnancy rates were assessed. Results In stepwise multiple logistic regression the variables with better predictiveness over pregnancy are: antral follicles count, estradiol and woman age. The logistic regression analyses demonstrate that the capacity of the model that uses these variables to predict pregnancy is 75%, with a positive predictive value of 69% and a negative predictive value of 80%. Conclusions On the fourth day of ovarian stimulation of IVF cycles, the variables with highest predictiveness are: antral follicle count, estradiol and women age. When these variables are included in a model of prediction, the capacity to predict pregnancy is 75%. On the fourth day of ovarian stimulation for IVF cycles, antral follicles count, estradiol and woman age predict IVF outcome as reflected by quantity and quality of oocytes, embryos obtained and pregnancy rates.     

Basal 17β-estradiol did not correlate with ovarian response and in vitro fertilization treatment outcome

Objective: To verify the correlation of basal 17β-E₂ with ovarian response to stimulation and outcome of in vitro fertilization (IVF).

Design: Retrospective observational study.

Setting: The Assisted Conception Unit, University College London Hospitals.

Patient(s): Three hundred five women undergoing IVF and IVF with intracytoplasmic sperm injection.

Intervention(s): Basal follicle-stimulating hormone (FSH) and 17β-E₂ were assessed. The cutoff level for day 2 E₂ established was 250 pmol/L. Each patient was noted for below (group A) or above (group B) the cutoff point according to her basal E₂ level.

Main Outcome Measure(s): Basal E₂, age, duration of infertility, cycle day 2 FSH, number of ampules of gonadotropin used, number of days of stimulation, number of retrieved oocytes, fertilization rate, number of embryos transferred, number of cycles with embryo freezing, cancellation rate, clinical pregnancy rate, and implantation rate were compared between the two groups.

Result(s): No differences were found between group A and group B in the number of oocytes retrieved (8.8 ± 4.2 vs. 9.3 ± 4.8), embryos transferred (2.5 ± 0.8 vs. 2.7 ± 0.7), cancellation (9.1% vs. 6.9%), pregnancy (24.8% vs. 30%), and implantation rate (12.3% vs. 15.6%). Correlation coefficient and coefficient of determination showed no significant correlation between basal E₂ and the number of oocytes retrieved, age, and basal FSH.

Conclusion(s): In our study population, basal E₂ was not a sensitive predictor of ovarian response to stimulation and did not correlate with IVF outcome.     

Endometrial receptivity in an in vitro fertilization program as assessed by spiral artery blood flow, endometrial thickness, endometrial volume, and uterine artery blood flow

OBJECTIVE: To investigate the role of sonographic parameters in assessing endometrial receptivity in an in vitro fertilization (IVF) program. DESIGN: Prospective clinical study. SETTING: University setting. PATIENT(S): One hundred thirty-five patients in our IVF program, selected prospectively on the day of oocyte retrieval. INTERVENTION(S): Transvaginal ultrasound examination was performed before oocyte collection. MAIN OUTCOME MEASURE(S): Association between implantation rate and spiral artery blood flow (primary outcome measure) and between implantation rate and endometrial measurements as well as uterine artery blood flow (secondary outcome measures). RESULT(S): Overall implantation rate was 23.7% per cycle. Subendometrial blood flow was detected in 113 (83.7%) cases, with pregnancy occurring in 21.2%. Mean spiral artery pulsatility index values were 1.12 +/- 0.28 and 1.21 +/- 0.27 for nonconception and conception cycles, respectively. Nondetectable spiral artery blood flow was not associated with a lower implantation rate. Neither endometrial thickness nor endometrial volume was correlated with the likelihood of successful implantation. Minimum endometrial thickness and volume associated with pregnancy were 6.9 mm and 1.59 mL, respectively. CONCLUSION(S): Neither Doppler sonography of the spiral or uterine arteries nor measurement of the endometrial thickness or volume allowed a reliable prediction of subsequent IVF outcome.     

Low serum estradiol concentrations after five days of controlled ovarian hyperstimulation for in vitro fertilization are associated with poor outcome

OBJECTIVE: To evaluate the prognostic significance of low serum E2 concentrations in controlled ovarian hyperstimulation (COH) cycles for IVF. DESIGN: Retrospective study. SETTING: Assisted conception unit of a university hospital. PATIENT(S): One thousand four hundred and forty patients undergoing COH for IVF. INTERVENTION(S): COH, serum E2 measurement, ultrasonographic scanning of ovarian follicles, oocyte retrieval, and ET. MAIN OUTCOME MEASURE(S): Cancellation and pregnancy rates. RESULT(S): Patients were classified into four groups according to serum E2 levels on the sixth day of COH: group A (E2 level < 50 pg/mL [114 cycles]), group B (E2 level 51-100 pg/mL [189 cycles]), group C (E2 level 101-200 pg/mL [320 cycles]), and group D (E2 level >200 pg/mL [817 cycles]). Group A experienced the highest cancellation rates (65.1%) and lowest pregnancy rates (7.8%) despite requiring significantly more hMG ampules (47.8+/-1.7). The cancellation rate was higher (75.1%) and no pregnancy occurred in a subset of group A in whom COH was initiated with > or =3 ampules (225 IU) of gonadotropins. CONCLUSION(S): In COH cycles using luteal phase buserelin, low initial serum E2 concentrations are associated with poor outcome.     

Inhibin B response to EFORT is associated with the outcome of oocyte retrieval in the subsequent in vitro fertilization cycle

Objective: To examine whether the magnitude of the rise in inhibin B levels after gonadotropin challenge is associated with subsequent response to ovarian stimulation during IVF.

Design: Inhibin B serum levels after EFORT (exogenous follicle-stimulating hormone ovarian reserve test).

Setting: Academic clinical practice.

Patient(s): Serum samples from women who had undergone ovarian reserve screening with FSH in preparation for IVF. Thirteen of these women had a poor response in IVF (canceled cycle for low estradiol and/or no oocytes retrieved), and 19 had a good response (≥10 oocytes retrieved).

Intervention(s): EFORT test.

Main Outcome Measure(s): Baseline (day 3) serum E₂ (bE₂), FSH (bFSH), and inhibin B (bInhB) levels and inhibin B and E₂ levels 24 hours after EFORT (ΔInhB and ΔE₂).

Result(s): The mean bInhB and ΔInhB levels were significantly higher in good vs. poor responders. The odds ratio of having a good response for women with a ΔInhB of 202 pg/mL was 51.8 times (95% CI = 6.1–1,244) the corresponding odds for women with a ΔInhB of 49 pg/mL. As expected, ΔE₂ was also significantly higher in good vs. poor responders; however, combination of ΔE₂ plus ΔInhB did not improve the odds for predicting IVF response.

Conclusion(s): Our data suggest that ΔInhB after EFORT may provide a method for predicting ovarian response to hyperstimulation in a subsequent IVF cycle.     

Is ABO blood type associated with ovarian stimulation response in patients with diminished ovarian reserve?

Purpose

Recent studies have explored the relationship between ABO blood type and serum markers of ovarian reserve, specifically follicle-stimulating hormone (FSH) and anti-mullerian hormone (AMH). The primary objective of this study is to investigate whether there is an association between ABO blood type and ovarian stimulation response in patients with serum markers of diminished ovarian reserve (DOR).

Methods

This is a retrospective study of all patients undergoing controlled ovarian stimulation (COS) for in vitro fertilization (IVF) between May 2010 and July 2013. Patients were sub-grouped, a priori, based on serum AMH levels: ≤1 ng/mL, ≤0.5 ng/mL and ≤0.16 ng/mL. Within each sub-group, demographic, baseline IVF characteristics and COS response parameters based on ABO blood types were compared. The number of mature oocytes retrieved was considered the primary outcome. Analysis of variance (ANOVA) and Chi-square tests were used to compare means and percentages between ABO blood types within groups.

Results

Complete data was available for 2575 patients. The mean (± SD) age and BMI of the study cohort was 38.9 (±3.97) years, 23.4 (±5.91) kg/m², respectively. The distribution of ABO blood types in the cohort was as follows: 36.8 % (A), 6.56 % (AB), 17.3 % (B), and 39.3 % (O). The demographics and baseline IVF characteristics were comparable among patients with blood types A, AB, B, and O within each AMH group. Within each AMH sub-group, no difference was found in the total days of COS, total gonadotropins administered, peak estradiol level, or number of mature oocytes retrieved based on blood type.

Conclusions

Our results suggest no association between ABO blood type and ovarian stimulation response in patients with DOR. The predictive value of ABO blood type in determining ovarian stimulation response in such patients is currently limited.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0485-3) contains supplementary material, which is available to authorized users.     

Age-specific levels for basal follicle-stimulating hormone assessment of ovarian function

OBJECTIVE: Traditionally, the most important measurement in the assessment of ovarian function has been age-independent baseline follicle-stimulating hormone (FSH) levels. The objective of this study was to characterize the continuum of ovarian function based on age-specific categories of baseline FSH. METHODS: In a cross-sectional historical cohort study we evaluated records of 434 patients with baseline FSH levels of less than 12 milli international units/mL that underwent ovulation induction for in vitro fertilization (IVF) with long gonadotropin-releasing hormone (GnRH) antagonist or GnRH agonist suppression and modal gonadotropin stimulation of 300 units of gonadotropins per day. In these patients with apparent normal ovarian function by current baseline FSH criteria and with routine ovarian stimulation, we assessed IVF cycle outcomes, including oocyte yields, based on age-specific baseline FSH levels, defined as levels less than or equal to the 95% confidence interval for each age group. RESULTS: Age-specific baseline FSH levels predicted the retrieval of fewer than or equal to four oocytes, with a positive predictive value of 19.5% and a negative predictive value of 88%. The Mantel-Haenszel common odds ratio for fewer than or equal to 4 oocyte production in the presence of premature ovarian aging was 2.8 (95% confidence interval 1.52-5.17; P<.001). CONCLUSION: These results suggest that, within generally accepted normal baseline FSH values, women with baseline FSH above the 95% confidence limits for age produce fewer oocytes in response to normal ovulation induction protocols compared with other women their age.     

Serum CA-125 and inhibin B levels in the prediction of ovarian response to gonadotropin stimulation in in vitro fertilization cycles

There is much controversy about the relationship between serum CA-125 levels during in vitro fertilization (IVF) cycles and ovarian function. To evaluate the prognostic value of serum CA-125 and inhibin B measurements in predicting ovarian response to gonadotropin stimulation, we compared the CA-125 and inhibin B levels of poor and normal responders on the first day of ovarian stimulation, on the day of ovulation induction (OI) and at oocyte pick-up. Sixteen patients with poor ovarian response (???3 oocytes, serum estradiol (E₂) ??900?pg/ml at OI) in IVF/intracytoplasmic sperm injection cycles were matched with normal responders (???6 oocytes, E₂ ??1800?pg/ml) by age, spontaneous cycle day-3 follicle-stimulating hormone level and cause of infertility. Inhibin B concentrations were significantly lower at all three time points in poor responders, but CA-125 levels were not. No statistically significant correlation was found between CA-125 levels and any of the clinical or laboratory parameters examined. Thus, CA-125 measurements during stimulation are not useful in predicting or identifying poor ovarian response to gonadotropin stimulation in IVF cycles. The lack of difference in CA-125 concentrations between poor and normal responders and lack of correlation with E₂ or inhibin B levels suggest that ovarian steroidogenesis and other granulosa cell functions do not influence the production of CA-125. Inhibin B, however, seems to predict ovarian response as early as at the start of stimulation.