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Repeated testing of basal FSH levels has no predictive value for IVF outcome in women with elevated basal FSH

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Abstract

It is a common practice to repeatedly test the level of basal FSH early in the cycle and to start IVF treatment only when the FSH level is below a certain threshold value. This is based on the idea that these women will respond better to ovarian stimulation when the basal FSH level is lower at the start of the cycle. The aim of this study is to assess the value of this practice. Between January 1995 and January 2003, 39 women were identified. These women underwent two IVF treatment cycles within a 12 month period. The basal FSH level prior to each of these cycles was known to have changed. The treatment cycles were divided into cycles with a high basal FSH (> or =10 IU/l) and cycles with a low basal FSH (<10 IU/l). The 39 women underwent a total of 78 treatment cycles (in the first cycle 20 had elevated level of FSH and 19 had low FSH and vice versa in the second cycle). Therefore, there were 39 cycles with high FSH and 39 cycles with low FSH. There was obviously no live birth in the first treatment cycle, hence the reason for the patient undergoing another treatment cycle within 12 months of the first one. In the high FSH group, six became pregnant [pregnancy rate (PR) = 15.4%] and five delivered [live birth rate (LBR) = 12.8%]. In the low FSH group, three became pregnant (PR = 7.7%) and two delivered (LBR = 5.1%). The difference in PR and LBR, however, was not significant. Neither were there significant differences between the two groups with regard to the number of oocytes collected, oocytes fertilized, embryos transferred or miscarriage rate. The results of this study reveal that women who are poor responders or with reduced ovarian reserve have a poor outcome and repeatedly testing them will add no value. Cycling women with a history of elevated FSH should be offered treatment without further delay. Delaying treatment for these women could be counterproductive, as they may have to wait for many months, during which time they are getting older and closer to their menopause.
Human Reproduction Vol.21, No.1 pp. 171–174, 2006 doi:10.1093/humrep/dei288
Advance Access publication September 9, 2005.
© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
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Repeated testing of basal FSH levels has no predictive value
for IVF outcome in women with elevated basal FSH
H.Abdalla
1
and M.Y.Thum
Lister Fertility Clinic, Lister Hospital, Chelsea Bridge Road, London SW1W 8RH, UK
1
To whom correspondence should be addressed. E-mail: sam@easynet.co.uk
BACKGROUND: It is a common practice to repeatedly test the level of basal FSH early in the cycle and to start IVF
treatment only when the FSH level is below a certain threshold value. This is based on the idea that these women will
respond better to ovarian stimulation when the basal FSH level is lower at the start of the cycle. The aim of this study
is to assess the value of this practice. METHODS: Between January 1995 and January 2003, 39 women were identi-
fied. These women underwent two IVF treatment cycles within a 12 month period. The basal FSH level prior to each
of these cycles was known to have changed. The treatment cycles were divided into cycles with a high basal FSH (10
IU/l) and cycles with a low basal FSH (<10 IU/l). RESULTS: The 39 women underwent a total of 78 treatment cycles
(in the first cycle 20 had elevated level of FSH and 19 had low FSH and vice versa in the second cycle). Therefore,
there were 39 cycles with high FSH and 39 cycles with low FSH. There was obviously no live birth in the first treat-
ment cycle, hence the reason for the patient undergoing another treatment cycle within 12 months of the first one. In
the high FSH group, six became pregnant [pregnancy rate (PR) = 15.4%] and five delivered [live birth rate (LBR) =
12.8%]. In the low FSH group, three became pregnant (PR = 7.7%) and two delivered (LBR = 5.1%). The difference
in PR and LBR, however, was not significant. Neither were there significant differences between the two groups with
regard to the number of oocytes collected, oocytes fertilized, embryos transferred or miscarriage rate. CONCLUSION:
The results of this study reveal that women who are poor responders or with reduced ovarian reserve have a poor
outcome and repeatedly testing them will add no value. Cycling women with a history of elevated FSH should be
offered treatment without further delay. Delaying treatment for these women could be counterproductive, as they
may have to wait for many months, during which time they are getting older and closer to their menopause.
Key words: basal stimulating hormone/FSH/IVF outcome/pregnancy rate
Introduction
The basal level of serum FSH is used as a screening test for
patients undergoing IVF. It is well documented that a high
day 3 basal level of FSH is associated with a lower pregnancy
rate (Sharif et al., 1998; El-Toukhy et al.,2002; Abdalla and
Thum, 2004). Indeed, some Units have been using this test to
screen patients with a lower chance of a pregnancy in view of
maintaining high clinic success rates (Sharif and Afnan,
2003).
It has also been a common practice to try to continue to
monitor the patient until such time that the FSH and estrodiol
levels fall below a certain point, indicating perhaps that the
ovary will be more responsive to stimulation. In these patients
they are subjected to repeated tests for day 3 basal FSH and the
treatment cycle will be started only if the basal FSH and estra-
diol are below certain cut-off levels.
Lass et al. (2000) suggested that, in patients with high basal
FSH, if the level returns to normal then the patient may have a
reasonable pregnancy rate. However, this has not been com-
pared with the chances of achieving a pregnancy when the
level of basal FSH remains high.
On the other hand, a high basal FSH level is perhaps reflec-
tive of reduced ovarian reserve (Scott et al., 1989). It has also
been suggested that if the FSH level is high on one or two
occasions then this may reflect the situation inside the ovary, in
which case waiting or not for that level to change will make no
substantial difference for the outcome (Scott et al., 1990).
In our department we treat any normally cycling woman
regardless of the level of her basal FSH and for those women with
elevated FSH we will counsel patients appropriately regarding the
realistic chance of conception (Abdalla and Thum, 2004). There-
fore we have patients being treated with high basal FSH and on
occasions their FSH may have been low as well. The question
remains as to whether patients with reduced ovarian reserve would
have the same response to medication if the treatment was affec-
ted in a cycle with lower basal FSH. We have searched through
the literature and there is no published work that looks at the same
patient to see whether the outcomes of two different treatment
cycles when the FSH was high or low were any different. We have
therefore decided to search our database for all patients who
underwent treatment cycles at least twice where on one occasion
the basal FSH was high and on the other the basal FSH was low.
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H.Abdalla and M.Y.Thum
172
The purpose of this study is to examine the hypothesis that
the outcome of IVF treatment in cycling women with reduced
ovarian reserve will not change whether the basal level of FSH
was above or below a certain threshold level.
Materials and methods
Data of patients undergoing IVF/ICSI treatment in our Unit are pro-
spectively routinely collected and stored (MedicalSys, London, UK).
Study population
We screened our database for women who underwent treatment cycles
for IVF/ICSI who have had the following criteria: two consecutive
cycles within 12 months; one cycle with FSH 10 IU/l and other cycle
with FSH <10 IU/l and estradiol <200 pmol/l.
Between January 1995 and January 2003, 39 women who under-
went 78 treatment cycles were identified. In these women the basal
FSH prior to each of these cycles was known to have changed. The
treatment cycles were divided into cycles with a high basal FSH (10
IU/l) and cycles with a low basal FSH (<10 IU/l). Each patient there-
fore acted as her own control. The level of 10 IU/l was found to be the
level above which there was a significant change in the pregnancy rate
from our previous study (Abdalla and Thum, 2004).
Treatment protocol
Ovarian stimulation was carried out with either recombinant FSH, HMG
or urinary FSH. A transvaginal scan was performed prior to ovarian stim-
ulation to ensure that the ovaries were quiescent. For the long protocol,
patients were down-regulated with either nafarelin or buserelin at mid-
luteal phase. For Cetrotide protocol, GnRH antagonist was commenced
when the leading follicle reached 12 mm. When follicles reached pre-ovu-
latory size (18–22 mm), 10 000 IU (for patients taking HMG)or 15 000 IU
(for patients taking FSH) of HCG was administrated. Oocytes were aspi-
rated using transvaginal ultrasound guidance 34–36 h after hCG adminis-
tration. Embryo transfer was performed on day 2 or day 3 using a soft
catheter with transabdominal ultrasound guidance. All patients received
progesterone 400 mg pessaries as supplement throughout the luteal phase.
A pregnancy test was performed 2 weeks after embryo transfer.
Data analysis
Data were collected in Medical System for IVF (MedicalSys, London,
UK) and analysed with Statistics Package for Social Sciences (SPSS,
Surrey, UK). Analysis of variance (ANOVA) was used to compare
means and χ
2
-test was used to analyse the significance of the differ-
ence between pregnancy rate and live birth rate. Associations between
FSH values with pregnancy rates, miscarriage rates and live birth rates
were examined with χ
2
cross-tabulation test. ANOVA was then con-
ducted to assess the relations between FSH levels with duration and
amount of gonadotrophin required to achieve follicular maturity,
number of mature follicles, number of available embryos for transfer,
number of oocytes collected and fertilization rate. Statistical signifi-
cance was set at P < 0.05.
Results
In total, 39 women underwent 78 treatment cycles (in the first
cycle 20 had elevated level of FSH and 19 had low FSH and
vice versa in the second cycle). Therefore, there were 39 cycles
with high FSH and 39 cycles with low FSH. There was obvi-
ously no live birth in the first treatment cycle, hence the reason
for the patient undergoing another treatment cycle within 12
months of the first. Patients were then grouped between cycles
in which the treatment cycle was performed when the FSH was
low, compared to those cycles in which the FSH was elevated.
The mean time lapsed between the two IVF cycles in the high
FSH group was 6.5 months (SD 4.3), whereas in the low FSH
group it was 6.5 months (SD 3.7) (not significant).
As can be seen in Table I, the only significant difference was
in relation to the level of FSH. There was no significant differ-
ence between both groups in relation to age, duration of infer-
tility, the total dose of gonadotrophins used, level of estradiol
at the time of HCG or the level of estradiol per follicle. The
numbers of oocytes collected, oocytes fertilized and embryos
transferred were also not significantly different between the
groups. Although the pregnancy and the live birth rate (LBR)
were lower in the normal FSH group, the difference was not
significant. A subgroup analysis was performed for good
responders (collected 4 oocytes) and poor responders (col-
lected <4 oocytes). The results showed that, within the poor
responder, there was no significant difference in terms of LBR
between the low FSH group (0%, n = 0/24) and high FSH
group (8%, n = 2/25). Likewise within the good responder, the
Table I. Treatment outcome in cycle with high or low basal FSH
a
Each patient underwent two treatment cycles and acted as their own control.
b
Mean amount of gonadotrophin used for stimulation in IU (recombinant FSH, HMG or urinary FSH).
NA = not applicable; NS = not significant.
High basal FSH Low basal FSH P
No. of cycles
a
39 39 NA
Basal FSH levels (prior to treatment cycle) (IU/l) [mean ± SD (range)] 13.9 ± 3.9 (0.5–10.0) 7.3 ± 2.3 (10.2–30.2) 0.001
Basal estradiol levels (prior to treatment cycle) (pmol/l) [mean ± SD (95% CI)] 135.9 ± 48.1 (120.3–151.5) 96.5 ± 76.9 (71.6–121.5) NS
Age (years) [mean ± SD (range)] 39.1 ± 3.4 (31–45) 39.2 ± 3.3 (32–45) NS
Mean duration of infertility in years [mean (95% CI)] 1.28 (0.44–2.13) 1.26 (0.43–2.07) NS
No. of previous failed IVF attempts [mean (95% CI)] 2.9 (2.32–3.58) 3.0 (2.33–3.67) NS
Gonadotrophin
b
(IU) (mean ± SD) 6718.4 ± 725.76 5911.7 ± 437.8 NS
Estradiol (pmol/l) on HCG day (mean ± SD) 3603.9 ± 2198.0 3228.1 ± 2901.0 NS
Estradiol (pmol/l) per follicle >13 mm (mean ± SD) 780 ± 467.0 823 ± 451.2 NS
Mean no. of stimulation days (95% CI) 16.08 (14.7–17.5) 15.49 (14.04–16.94) NS
Mean no. of oocytes collected (95% CI) 4.5 (3.76–5.32) 4.2 (3.23–5.24) NS
Mean no. of embryos transferred (95% CI) 1.74 (1.41–2.08) 1.56 (1.18–1.95) NS
Pregnant [no. (%)] 6 (15.4) 3 (7.7) 0.294
Live birth [no. (%)] 5 (12.8) 2 (5.1) 0.240
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Repeat basal FSH testing and IVF outcome
173
LBR was not significantly different between the low FSH
group (13.3%, n = 2/15) and high FSH group (21.4%, n = 3/14).
Further subgroup analysis was conducted with regard to
women’s age. There were only eight women with aged <35
years; none of them had a successful live birth regardless of the
FSH levels. For women aged >35 years, the LBR for the high
FSH group was 15.6% (n = 5/32) and for the low FSH group
was 6.5% (2/31) (not significant).
Discussion
This is, to our knowledge, the first study ever to evaluate the
difference in the outcome of assisted conception treatment
cycles in the same patient, with a diagnosis of reduced ovarian
reserve, when treatment cycles were initiated with differing
levels of basal FSH. Scott and Hofmann (1995) in a review art-
icle suggested that serial screening of FSH levels to select the
optimal cycle for stimulation would be of limited value; this
suggestion is in accord with the findings of our study. This
study, in our view, provides a specific answer to the question
as to whether repeated testing of FSH for patients to bring their
basal FSH levels down to what is presumed to be an acceptably
low level will be beneficial for the patient’s treatment. In this
study we not only examined the level of basal FSH, but we
insisted that if the basal FSH level was low, we wanted the
level of estrodiol also to be low to exclude the possibility that
the FSH was brought down because of a high circulating level
of estradiol. Although different types of gonadotrophins and
agonist or antagonist protocols were used for stimulation, this
should have had no effect on the outcome of ovulation induc-
tion as there is strong evidence in the literature suggesting that
different gonadotrophins and agonist or antagonist protocols
ultimately have the same effect on follicular development
(Agrawal et al., 2000; Borm and Mannaerts, 2000; Van Wely
et al., 2003; Mohamed et al., 2005). Whether the long protocol
or Cetrotide protocol was used, the FSH which was measured
was the nearest to the cycle. There was no attempt to insist that
the FSH measurement be performed in the same cycle in which
treatment was performed but the nearest value to that cycle was
used. Nevertheless we believe that the value of FSH, though
not in the actual cycle in which treatment was performed,
reflects the state of the ovary at the time the ovulation induc-
tion regime was started. We have also limited our study to a 12
month period to negate the effect of ageing and also to exclude
any patients who had had a live birth in their first cycle.
Although not all FSH levels were checked within the same cycle,
they were checked in the cycle before the treatment, which is the
common practice in the UK when the patient was having IVF
treatment with the long protocol. However, from our data we
have 19 paired cycles which the FSH levels were checked within
the same cycle and the outcome was similar to that we reported;
with live birth rate of 15.8 (3/19) in cycle started with high FSH
and 5.3% (1/19) in cycle started with low FSH.
It is possible, of course, that all of these patients might have
had a low inhibin B level, which works independently of the
levels of both their FSH and estrodiol. However, this is not
routinely measured in our department and therefore is not part
of this analysis. These findings nevertheless are rather import-
ant because the measurement of FSH and estrodiol are the most
commonly used to screen patients prior to treatment and a pre-
vious study by Creus et al. (2000) suggested that basal FSH is
a stronger predictor of ovarian reserve than inhibins.
We have shown in a previous study that the elevation of the
level of basal FSH reflects a reduced ovarian reserve (Abdalla
and Thum, 2004). This reduction of ovarian reserve is in fact a
permanent condition and it is therefore illogical to presume
that if the total number of oocytes in the ovary is reduced that
they will miraculously change in number if the level of FSH is
reduced. The study, however, shows that there are patients
with occult reduced ovarian reserve as evidenced by those who
had normal FSH level in their first cycle. These patients had a
raised FSH in the second cycle and still responded in the same
fashion to the medications; therefore, repeat testing of basal
FSH level has no benefit in women with reduced ovarian
reserve and in fact it is counterproductive in view of losing
reproductive time. This suggestion is in accord with a previous
study (Bancsi et al., 2004) showing that repeat measurements
of basal FSH levels have no clinical value.
The responsiveness of the ovary is determined primarily by
the number of primordial follicles, rather than by mere
changes in the hormones. The level of basal FSH, however, is
an indirect indication of that reduction in ovarian reserve. This
suggestion is in accord with previous studies (Bancsi et al.,
2000; Frattarelli et al., 2000) showing that reduced antral folli-
cle count, as related to a reduced quantity of primordial folli-
cles, is a better indicator of ovarian reserve than basal FSH
levels. In this study we examined patients who on average had
three failed IVF attempts and primary infertility. One may
argue that this may skew the results to severe cases and as such
the results may not be representative of all patients with ele-
vated FSH; nevertheless there is no evidence to suggest that
women with elevated FSH achieve better outcomes in their
earlier rather than their latter attempts. Furthermore, this study
does provide evidence that in a good controlled situation with
an equal number of failed attempts, the chances of conception
and implantation are no different whether the FSH was high
or low.
In our view, cycling women with reduced ovarian reserve
deserve to be treated; they do have a reasonable chance of
achieving a pregnancy (Abdalla and Thum, 2004). What is
important is that they are informed of their lower chance to
achieve a pregnancy compared to their counterpart with normal
ovarian reserve. Continued hunting for a change in the level of
basal FSH is rather counterproductive, as they may be waiting
for many months for that change in the level of FSH to occur,
during which time they are getting older and nearer to their
menopause. It would therefore be appropriate to treat them if
they are normally cycling with the full knowledge that their
chances of achieving a pregnancy are not particularly high.
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Submitted on February 10, 2005; revised on June 12, 2005; accepted on July
28, 2005
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... The higher level of FSH in older women is indicative of decreased ovarian reserve. A study reported that there were no significant differences in level of FSH with age (23) . When we There were studies which were in agreement with our finding in that the elevated FSH level is associated with poor ICSI outcome (7,12,24) . ...
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... Tỷ lệ có thai chỉ dưới 2% nếu nồng độ FSH cơ bản đến 25 mIU/ml.Tuy nhiên, nhiều trường hợp có tăng nồng độ FSH cơ bản nhưng khả năng đáp ứng của buồng trứng vẫn tốt, tỷ lệ có thai 16% mỗi noãn khi có trên 3 noãn ở những phụ nữ trên 40 tuổi (Bassil, 1999) và tỷ lệ có thai diễn tiến cao mặc dù tỷ lệ hủy chu kỳ điều trị cao hơn những người có nồng độ FSH bình thường (van Rooij, 2003). Việc định lượng FSH cơ bản có thể thực hiện nhiều lần nhưng điều này không đem lại lợi ích gì (Abdalla, 2006). Phân tích tổng hợp cho thấy FSH có giá trị dự báo trung bình đối với đáp ứng buồng trứng và hiệu quả IVF . ...
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Thesis
Full-text available
This thesis examines the various interventions proposed for the management of poor responders undergoing IVF treatment. I began by performing a systematic review and meta-analysis to identify the ideal controlled ovarian hyperstimulation (COH) regimen for women with poor ovarian response undergoing IVF. The systematic review found the evidence to be inconsistent and inconclusive. The poor responders intervention trial (PRINT) was thus conceived. PRINT is an RCT comparing the gonadotrophin releasing hormone (GnRH) agonist long versus the GnRH agonist short versus the GnRH antagonist regimens for poor responders undergoing IVF. Results of PRINT showed the GnRH agonist long regimen to be efficacious. The relationship between egg numbers and live birth following IVF is poorly understood. I set out to investigate this by examining a large cohort of IVF cycles. I was able to demonstrate a strong association between egg numbers and live birth following IVF and justify the use of egg numbers as a primary outcome for PRINT. A frequent scenario faced in the management of women who have a poor response is whether to continue with their current IVF cycle or to cancel and start again on the assumption that there could be intercycle variability. I examined this hypothesis by comparing two consecutive IVF cycles with identical COH regimens. There was no significant intercycle variability in poor responders suggesting that the more cost effective option would be to continue with the IVF cycle Over the last decade a number of studies have been published on the use of androgen supplementation in poor responders. I conducted a systematic review and meta-analysis which demonstrated potential benefit from androgen supplementation but highlighted the shortcomings in the existing evidence. Finally, I conclude my thesis by examining the evidence behind some common clinical practices in the management of poor responders with suggestions for future research.
Chapter
In the normal ovulatory cycle, the recruited cohort of antral follicles can be identified by cycle day 5–7, the dominant follicle emerges by day 8–12, grows approximately 1–3 mm per day thereafter (most rapidly over the 1–2 days immediately preceding ovulation), and measures approximately 20–24 mm in mean diameter when the luteinizing hormone (LH) surge occurs; lesser follicles rarely exceed approximately 14 mm in diameter. In 5–10 % of spontaneous cycles, two preovulatory follicles may develop. The ultrasound examination enables the follicle diameter and endometrial thickness to be measured, which evaluates the fecundity function by using blood-flow assessment and the combined three dimensional (3D) and blood-flow investigation. Ovarian ultrasonography defines the size and number of follicles contributing to the measured estradiol (E2) level. Thus, in an ovulation induction cycle, ultrasound can tell us about the ovarian reserve and adequately monitor the process of downregulation, follicular and endometrial development, and timely administration of human chorionic hormone (hCG), with an increase in the overall pregnancy rates and decrease in the incidence of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy rate. Baseline follicular stimulating hormone (FSH), antiMullerian hormone (AMH), and inhibin B levels on day 2 or 3 on menstrual cycle and dynamic tests can give information about the ovarian reserve. Monitoring LH, E2, and progesterone during ovulation induction can determine the follicular growth and its competency, predict poor and hyper-response, and diagnose premature LH surge, premature luteinization and luteal phase adequacy.
Article
Objective: To determine the predictive value and define threshold levels for basal antral follicle number and mean ovarian diameter in patients undergoing ART cycles. Design: Retrospective. Setting: Tertiary care center. Patients: Two hundred seventy-eight patients who had ovarian measurements performed on cycle day 3 before beginning treatment with gonadotropins. Intervention: Pretreatment ovarian ultrasound measurements. Main outcome measure: Number of oocytes retrieved, hormone levels, and cycle outcomes. Results: A direct linear correlation was observed between mean ovarian diameter and basal follicle number. Both measures demonstrated a positive linear correlation with recovered oocytes, basal E(2), and peak E(2). Both demonstrated a negative linear correlation with ampules of gonadotropins administered, days of stimulation, patient age, cycle day 3 FSH, and FSH:LH ratio. An antral follicle count of </=10 or a mean ovarian diameter of <20 mm was associated with an increased risk of cycle cancellation. Conclusions: Ovarian diameter and basal antral follicle number identify patients who may respond poorly to ART stimulation. These ovarian measures correlate well with ART screening and stimulation parameters. This knowledge allows physicians to evaluate and counsel patients immediately before an ART stimulation and to optimize stimulation protocols.
Article
Objective To examine the relative effect of basal follicle stimulating hormone (FSH) concentration and the woman's age on predicting the ovarian response to gonadotrophin stimulation, normal fertilisation rate and pregnancy rate in in vitro fertilisation (IVF) treatment following pituitary desensitisation. Design Descriptive cohort study. Participants Three hundred and forty-four women undergoing their first IVF cycle. Methods Basal (menstrual-day 3) FSH concentration was measured and the woman's age calculated before she underwent pituitary desensitisation followed by gonadotrophin ovarian stimulation and IVF treatment. Main outcome measures Cancellation rate due to poor ovarian response, total dose of gonadotrophin required to achieve follicular maturity, number of oocytes collected, normal fertilisation rate and pregnancy rate were compared between banded values of the variables studied. Results Increasing basal FSH concentration was associated significantly with increased cancellation rate, but increasing age was not. Both increasing basal FSH and age were associated significantly with increased total gonadotrophin dose, and reduced number of oocytes collected and pregnancy rate. Analysis of variance showed that the association for basal FSH with the number of oocytes was significant, independent of, and stronger than the effects of age. Logistic regression analysis showed that age, but not basal FSH, was independently associated with pregnancy rate. Neither basal FSH, nor age had significant association with normal fertilisation rate. Conclusion Basal FSH concentration is a better predictor of cancellation rate and of the number of oocytes collected in IVF treatment than age, but age is a stronger predictor of pregnancy rate.
Article
Prior studies have demonstrated that gonadotropin stimulation quality and pregnancy rates are better in in vitro fertilization (IVF) patients with low basal cycle day 3 follicle-stimulating hormone (FSH) levels. The records of 81 patients who had undergone three or more IVF attempts during a 2-year period were studied to determine the degree and potential impact of intercycle variability in basal FSH concentrations. The mean of the individual standard deviations for all 81 patients was 4.2 +/- 0.4 mIU/mL. However, the patients with a mean basal FSH of less than 15 mIU/mL had a mean deviation of only 2.6 +/- 0.2 mIU/mL, whereas those with a mean basal FSH of greater than or equal to 15 mIU/mL had a mean deviation of 7.3 +/- 0.7 mIU/mL. Intercycle variability in basal FSH values did not predict changes in ovarian response to gonadotropin stimulation and thus may not be used to select an optimal cycle in which to stimulate an individual patient. Furthermore, patients with large intercycle variation responded poorly to gonadotropin stimulation independent of their basal FSH concentration. This information allows more precise counseling of patients regarding their appropriateness for assisted reproduction.
Article
Cycle day 3 basal levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured in 441 patients in 758 consecutive cycles to determine their predictive value for stimulation quality and pregnancy rates in vitro fertilization (IVF). Patients with low basal FSH levels (less than 15 mIU/ml) had higher pregnancy rates per attempt than those with moderate levels (15 to 24.9 mIU/ml), both of which were higher than those with high FSH levels (greater than 25 mIU/ml). Basal LH and E2 values did not improve the predictive value beyond that provided by FSH. Ongoing pregnancy rates per attempt in the low, moderate, and high FSH groups were 17.0%, 9.3%, and 3.6%, respectively (P less than 0.01). The three groups differed significantly in the percentage of patients having two ovaries, the mean number of follicles aspirated per retrieval, the mean number of preovulatory oocytes obtained, and peak E2 values (P less than 0.01). Cycle day 3 FSH levels are predictive of pregnancy outcome and stimulation characteristics in IVF, and may be useful in counseling patients.
Article
To review the literature regarding diminished ovarian reserve, the screening techniques that are currently available, and their appropriate application in clinical practice. Directed Medline searches. Ovarian reserve screening identifies women with greatly diminished chances of achieving pregnancy. The screening techniques include the clomiphene citrate challenge test, basal day 3 FSH measurements, and the GnRH agonist stimulation test. All have been evaluated in assisted reproduction programs and the predictive values of an abnormal test for failing to conceive is very high. When abnormal, these tests allow physicians to counsel patients that their prognosis for conception is poor. Although the presence of a normal result does indicate better long-term chances for conception, an age-related decline in fecundity remains and patient age should still be considered when counseling patients with normal screening results. Clinicians are urged to validate the threshold values with the assay system used in their own laboratory before the application of these tests. The literature consistently demonstrates the value of diminished ovarian reserve screening.
Article
To examine the relative effect of basal follicle stimulating hormone (FSH) concentration and the woman's age on predicting the ovarian response to gonadotrophin stimulation, normal fertilisation rate and pregnancy rate in in vitro fertilisation (IVF) treatment following pituitary desensitisation. Descriptive cohort study. Three hundred and forty-four women undergoing their first IVF cycle. Basal (menstrual-day 3) FSH concentration was measured and the woman's age calculated before she underwent pituitary desensitisation followed by gonadotrophin ovarian stimulation and IVF treatment. Cancellation rate due to poor ovarian response, total dose of gonadotrophin required to achieve follicular maturity, number of oocytes collected, normal fertilisation rate and pregnancy rate were compared between banded values of the variables studied. Increasing basal FSH concentration was associated significantly with increased cancellation rate, but increasing age was not. Both increasing basal FSH and age were associated significantly with increased total gonadotrophin dose, and reduced number of oocytes collected and pregnancy rate. Analysis of variance showed that the association for basal FSH with the number of oocytes was significant, independent of, and stronger than the effects of age. Logistic regression analysis showed that age, but not basal FSH, was independently associated with pregnancy rate. Neither basal FSH, nor age had significant association with normal fertilisation rate. Basal FSH concentration is a better predictor of cancellation rate and of the number of oocytes collected in IVF treatment than age, but age is a stronger predictor of pregnancy rate.
Article
To reanalyze the results of using FSH alone and hMG during IVF treatment, taking into account the different protocols of administration of superactive GnRH agonist analogs. Meta-analysis. The London Women's Clinic. Women undergoing IVF treatment. A meta-analysis of published randomized controlled trials from 1985 to 1999 of the use of FSH versus hMG for ovarian stimulation during IVF treatment. The common Peto odds ratio was calculated with use of a fixed effect model. The overall log odds ratio was estimated after demonstrating the consistency or homogeneity of the study results. Clinical pregnancy rate per cycle of IVF. The results suggested that in the "long and short GnRH agonists protocol" of IVF, FSH, and hMG were equally effective in achieving ovarian stimulation, and there were no differences in the clinical pregnancy rates per cycle of IVF. However, in protocols where no pituitary desensitization was used, FSH alone was more efficacious. The optimum choice of gonadotropin preparation for ovarian stimulation during IVF treatment is influenced by the regimen of pituitary desensitization used. The optimum gonadotropin to be used when GnRH antagonists are used has yet to be determined.
Article
Objective: To evaluate whether basal FSH (bFSH; measured on menstrual day 1-4) adds relevant clinical information to the prediction of ongoing pregnancy rates (OPRs) after IVF, once age and diagnostic characteristics have been taken into account. Design: Retrospective. Setting: Academic fertility center. Patient(s): 435 women undergoing their first IVF cycle. Intervention(s): None. Main outcome measure(s): Ongoing pregnancy rate. Result(s): The likelihood ratio of bFSH as a single prognosticator for treatment failure at a cutoff level of 15 IU/L was 3.87. The proportion of patients with such a bFSH level was 5%. Multivariate logistic regression analysis selected age, bFSH level, and infertility diagnosis as relevant predictors of ongoing pregnancy. When compared to a predictive model for OPRs based on age and infertility diagnosis, the inclusion of bFSH into this model helped to identify more patients (22 vs. 1) whose predicted OPR decreased from a low level (5%-12%) towards an extremely low level (<5%). Conclusion(s): An acceptable performance of bFSH as a single test to predict treatment failure is only obtained above a high cutoff level. Thus, the number of patients for whom bFSH provides relevant information is small. The predictive model including bFSH identified significantly more patients with an extremely poor prognosis than did the predictive model without bFSH. However, predictions based solely on age and infertility diagnosis usually were already poor in these patients. Measurement of bFSH adds little in only a few patients and is, therefore, debatable.
Article
A multicentre, open-label, randomized study of the gonadotrophin-releasing hormone (GnRH) antagonist ganirelix (Orgalutran((R))/Antagon((TM))) was performed in women undergoing ovarian stimulation with recombinant FSH (rFSH: Puregon((R))). The study was designed as a non-inferiority study using a long protocol of buserelin (intranasal) and rFSH as a reference treatment. A total of 730 subjects was randomized in a treatment ratio of 2:1 (ganirelix:buserelin) using an interactive voice response system which stratified for age, type of infertility and planned fertilization procedure [IVF or intracytoplasmic sperm injection (ICSI)]. The median duration of GnRH analogue treatment was 5 days in the ganirelix group and 26 days in the buserelin group, whereas the median total rFSH dose was 1500 IU and 1800 IU respectively. In addition, in the ganirelix group the mean duration of stimulation was 1 day shorter. During ganirelix treatment the incidence of LH rises (LH >/=10 IU/l) was 2.8% versus 1.3% during rFSH stimulation in the buserelin group. On the day of triggering ovulation by human chorionic gonadotrophin (HCG), the mean number of follicles >/=11 mm diameter was 10.7 and 11.8, and the median serum oestradiol concentrations were 1190 pg/ml and 1700 pg/ml in the ganirelix and buserelin groups respectively. The mean number of oocytes per retrieval was 9.1 and 10.4 respectively, whereas the mean number of good quality embryos was 3.3 and 3.5 respectively. The fertilization rate was equal in both groups (62.1%), and the same mean number of embryos (2.2) was replaced. The mean implantation rates were 15.7% and 21.8%, and the ongoing pregnancy rates per attempt were 20.3% and 25.7% in the ganirelix and buserelin groups respectively. Evaluation of all safety data indicated that the ganirelix regimen was safe and well tolerated. The overall incidence of ovarian hyperstimulation syndrome was 2.4% in the ganirelix group and 5.9% in the reference group. The results of this study support a safe, short and convenient treatment regimen of ganirelix, resulting in a good clinical outcome for patients undergoing ovarian stimulation for IVF or ICSI.
Article
To determine the predictive value and define threshold levels for basal antral follicle number and mean ovarian diameter in patients undergoing ART cycles. Retrospective. Tertiary care center. Two hundred seventy-eight patients who had ovarian measurements performed on cycle day 3 before beginning treatment with gonadotropins. Pretreatment ovarian ultrasound measurements. Number of oocytes retrieved, hormone levels, and cycle outcomes. A direct linear correlation was observed between mean ovarian diameter and basal follicle number. Both measures demonstrated a positive linear correlation with recovered oocytes, basal E(2), and peak E(2). Both demonstrated a negative linear correlation with ampules of gonadotropins administered, days of stimulation, patient age, cycle day 3 FSH, and FSH:LH ratio. An antral follicle count of </=10 or a mean ovarian diameter of <20 mm was associated with an increased risk of cycle cancellation. Ovarian diameter and basal antral follicle number identify patients who may respond poorly to ART stimulation. These ovarian measures correlate well with ART screening and stimulation parameters. This knowledge allows physicians to evaluate and counsel patients immediately before an ART stimulation and to optimize stimulation protocols.