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An elevated basal FSH reflects a quantitative rather than qualitative decline of the ovarian reserve

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Abstract

Many cycling women with elevated basal FSH level have been discouraged from undergoing IVF treatment. This is because elevated basal FSH is associated with poorer assisted reproduction treatment outcome. It has been argued that high FSH reflects not only reduced ovarian reserve but also poor oocyte quality. The aim of this study is to assess the value of treating cycling women who have elevated basal FSH and to assess the reasons for the reduction in both pregnancy rate (PR) and live birth rate (LBR). Between January 1997 and December 2001, 2057 patients underwent 3401 consecutive IVF/ICSI cycles in which the basal level of FSH (days 2-4) was determined at an earlier cycle. Analysis, however, was only performed for a single cycle per patient. All cases were divided into four cohorts according to FSH levels: group A, FSH <10 IU/ml; group B, 10.1-15 IU/ml; group C, 15.1-20 IU/ml; and group D, FSH >20 IU/ml. Each group was stratified further into subgroups according to age, < or =38 and >38 years. Both PR (A, 32.3%; B, 19.8%; C, 17.5%; and D, 3%) and LBR (A, 24.7%; B, 13.2%; C, 13.8%; and D, 3%) were significantly reduced in the higher FSH level groups. LBR was significantly higher in the younger subgroups (A, 32.2%; B, 21.8%; C, 20%; and D, 16.7%) as compared with the older subgroups (A, 12.1%; B, 8.3%; C, 10.5%; and D, 0%). Higher levels of FSH were significantly associated with more cycle cancellation, a larger amount of gonadotrophin required to achieve follicular maturity, and a lower number of eggs collected, embryos available and embryos transferred. In all cases, however, there was no significant correlation between FSH levels and fertilization rate or miscarriage rate. Younger cycling women with elevated FSH had significantly higher LBR compared with older women with normal FSH (21.2% versus 12.1%). Furthermore, the cumulative LBR after three cycles in these younger patients with elevated FSH levels was 49.3%. Although there is a reduction in both PR and LBR associated with higher levels of basal FSH, it is clear that in cycling women, high basal FSH is not a contraindication to IVF treatment, and a respectable PR and LBR can be achieved especially in young women. The reduction in PR and LBR is due to reduced reserve rather than poor oocyte quality. Clinics refusing to treat cycling women with elevated basal FSH levels may be denying these women a reasonable, albeit low, chance of achieving a birth with their own genetic material. Clinicians should use basal FSH levels as a guide to advise patients about their chances of achieving a live birth, not to exclude patients with a predicted lower success rate from a treatment programme.
Advance Access publication March 11, 2004
An elevated basal FSH re¯ects a quantitative rather than
qualitative decline of the ovarian reserve
H.Abdalla
1
,
2
and M.Y.Thum
1
1
Lister Fertility Clinic, Lister Hospital, Chelsea Bridge Road, London SW1W 8RH, UK
2
To whom correspondence should be addressed. E-mail: sam@easynet.co.uk
BACKGROUND: Many cycling women with elevated basal FSH level have been discouraged from undergoing IVF
treatment. This is because elevated basal FSH is associated with poorer assisted reproduction treatment outcome. It
has been argued that high FSH re¯ects not only reduced ovarian reserve but also poor oocyte quality. The aim of
this study is to assess the value of treating cycling women who have elevated basal FSH and to assess the reasons for
the reduction in both pregnancy rate (PR) and live birth rate (LBR). METHODS: Between January 1997 and
December 2001, 2057 patients underwent 3401 consecutive IVF/ICSI cycles in which the basal level of FSH (days
4) was determined at an earlier cycle. Analysis, however, was only performed for a single cycle per patient. All cases
were divided into four cohorts according to FSH levels: group A, FSH <10 IU/ml; group B, 10.1±15 IU/ml; group C,
15.1±20 IU/ml; and group D, FSH >20 IU/ml. Each group was strati®ed further into subgroups according to age,
<38 and >38 years. RESULTS: Both PR (A, 32.3%; B, 19.8%; C, 17.5%; and D, 3%) and LBR (A, 24.7%; B,
13.2%; C, 13.8%; and D, 3%) were signi®cantly reduced in the higher FSH level groups. LBR was signi®cantly
higher in the younger subgroups (A, 32.2%; B, 21.8%; C, 20%; and D, 16.7%) as compared with the older sub-
groups (A, 12.1%; B, 8.3%; C, 10.5%; and D, 0%). Higher levels of FSH were signi®cantly associated with more
cycle cancellation, a larger amount of gonadotrophin required to achieve follicular maturity, and a lower number of
eggs collected, embryos available and embryos transferred. In all cases, however, there was no signi®cant correl-
ation between FSH levels and fertilization rate or miscarriage rate. Younger cycling women with elevated FSH had
signi®cantly higher LBR compared with older women with normal FSH (21.2% versus 12.1%). Furthermore, the
cumulative LBR after three cycles in these younger patients with elevated FSH levels was 49.3%. CONCLUSION:
Although there is a reduction in both PR and LBR associated with higher levels of basal FSH, it is clear that in cyc-
ling women, high basal FSH is not a contraindication to IVF treatment, and a respectable PR and LBR can be
achieved especially in young women. The reduction in PR and LBR is due to reduced reserve rather than poor
oocyte quality. Clinics refusing to treat cycling women with elevated basal FSH levels may be denying these women
a reasonable, albeit low, chance of achieving a birth with their own genetic material. Clinicians should use basal
FSH levels as a guide to advise patients about their chances of achieving a live birth, not to exclude patients with a
predicted lower success rate from a treatment programme.
Key words: basal stimulating hormone/FSH/IVF/IVF outcome/pregnancy rate
Introduction
Determination of ovarian reserve by measuring day 3 basal
FSH in normal cycling women is often used in many IVF units
prior to assisted conception treatment to choose patients
eligible for starting assisted reproduction technique (ART)
cycles. Many cycling women with borderline elevated basal
FSH have been discouraged from undertaking ART treatment
because the chance of success is thought to be low, and have
been directed to other modalities such as oocyte donation or
adoption.
The cycle day 3 FSH level is one of the most commonly
used tests for predicting success in IVF treatment. This was
®rst described by Muasher et al. (1988). Lenton et al.
(1988) demonstrated that women with an elevated cycle day
3 FSH had reduced ovarian reserve. Since then, several
studies have shown that women with an elevated FSH level,
independent of age, have a poor response to ovarian
stimulation, leading to a lower pregnancy rate with ART
(Scott et al., 1989; Martin et al., 1996; Sharif et al., 1998;
El-Toukhy et al., 2002). Recently, however, El-Toukhy et al.
(2002) argued that young age does not protect against the
adverse effects of reduced ovarian reserve, suggesting that
an elevated day 3 basal FSH level is associated not only
with a low response, but also with poor quality oocytes
leading not only to a reduction in pregnancy rate but also to
a rise in miscarriage rates.
Human Reproduction Vol.19, No.4 pp. 893±898, 2004 DOI: 10.1093/humrep/deh141
Human Reproduction vol. 19 no. 4
ã
European Society of Human Reproduction and Embryology 2004; all rights reserved 893
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Recently some studies have shown that women with
elevated basal FSH levels can still achieve reasonable preg-
nancy rates with ART (Levi et al., 2001; Esposito et al., 2002;
van Rooij et al., 2003), especially in younger women. Those
cycling women who are discouraged from undertaking treat-
ment may, therefore, be denied a reasonable chance of
achieving a pregnancy with their own genetic child. In our
department, we operated on the principle that if the woman was
cycling regularly, then we should offer ART regardless of the
basal level of FSH. The purpose of this study is to assess the
value of treating cycling women who have an elevated basal
FSH and to evaluate the hypothesis that the lower pregnancy
rate in cycling women with elevated basal FSH levels is due to
a reduced ovarian reserve (re¯ected by cancellation rate, dose
of gonadotrophins used to stimulate the ovaries and number of
eggs collected) rather than poor oocyte quality (re¯ected by
fertilization and miscarriage rates). This would help the patient
understand that if they managed to get to the stage of egg
collection and eggs were obtained, then their chance of having
these eggs fertilized normally would be similar to that of any
other couple and that their chance of becoming pregnant was
similar to that of women of their own age with a similar number
of embryos generated. Moreover, should their cycle result in a
pregnancy, it would not be at higher risk of miscarriage.
Materials and methods
Data of patients undergoing IVF/ICSI treatment in our unit are
routinely collected prospectively and stored in a system for IVF
(MedicalSys, London, UK).
Study population
Between January 1997 and December 2001, all patients underwent
IVF/ICSI treatment. The most recent basal FSH level (days 2±4 of the
menstrual cycle) was determined in a cycle prior to the start of IVF/
ICSI treatment. There was no attempt to check the level of FSH in the
treatment cycle itself. Patients were treated with either a long or short
protocol. All patients, regardless of age or FSH levels, underwent
ovarian stimulation.
Serum FSH level test
Serum FSH concentration was measured using a two-step chemilu-
minescent microparticle immunoassay (CMIA) and analysed by
Abbott Architect
Ô
System (Abbott Laboratories, IL). The analytical
sensitivity of the assay was calculated to be better than 0.05 mIU/ml
(n = 36 runs). Analytical sensitivity is de®ned as the concentration at 2
SDs from the ARCHITECT FSH MasterCheck
Ô
Level 0 (0.00 mIU/
ml), and represents the lowest measurable concentration of FSH that
can be distinguished from zero. The speci®city of the assay was
determined by studying the cross-reactivity of LH, thyroid-stimulating
hormone (TSH) and HCG. The percentage cross-reactivity was
calculated and was shown to be 0.002% for LH, 0.043% for TSH and
0.001% for HCG. The inter- and intra-assay coef®cients of variation
were 2.9 and 3.8%, respectively.
Treatment protocol
Ovarian stimulation was carried out with either recombinant FSH,
HMG or urinary FSH. A transvaginal scan was performed prior to
ovarian stimulation to ensure the ovaries were quiescent. For the long
protocol, patients were downregulated with either Nafarelin or
Buserelin at mid-luteal phase. For the Cetrotide protocol, GnRH
hormone antagonist was commenced when the leading follicle
reached 12 mm. When follicles reached pre-ovulatory size (18±
22 mm), 10 000 IU (for patients taking HMG) or 15 000 IU (for
Table I. Stimulation characteristics and cycle outcome
Group A
(FSH <10.1 IU/l)
Group B
(FSH 10.1±15 IU/l)
Group C
(FSH 15.1±20 IU/l)
Group D
(FSH >20 IU/l)
No. of patients 1721 245 58 33
Mean age 6 SD
b
35.8 6 4.7 38.2 6 4.4 38.8 6 4.4 40.3 6 4.8
Duration of infertility (mean 6 SD)
b
4.45 6 3.7 4.57 6 4.1 3.94 6 2.69 4.21 6 3.87
Cancellation rate (%)
a
6.1 14.0 32.8 42.4
Days of taking gonadotrophins (mean 6 SD)
b
11.7 6 2.9 11.8 6 2.9 11.9 6 4.0 11.6 6 3.8
No of ampoules
c
consumed (mean 6 SD)
d
37.6 6 15.6 49.4 6 18.7 51.0 6 17.2 49.1 6 21.6
Estradiol (IU) per follicle on HCG day
e
423.1 417.8 452.3 683.9
Average no. of oocytes collected
d
9.9 5.6 3.8 2.5
Fertilization rate (%)
e,f
59.5% 58.3% 60.9% 62.0%
Average no of available embryos for transfer
d
5.53 3.14 2.92 2.15
Average no of embryos transferred
d
2.20 1.82 1.63 1.05
Pregnancy rate per started cycle in % (n)
b
32.3 (554/1721) 19.8 (48/245) 17.5 (10/58) 3.0 (1/33)
LBR per started cycle in % (n)
b
24.7 (425/1721) 13.2 (32/245) 13.8 (8/58) 3.0 (1/33)
Pregnancy rate per egg collection in % (n)
b
34.3 (554/1615) 23.0 (48/209) 25.6 (10/39) 5.3 (1/19)
LBR per egg collection in % (n)
b
26.3 (425/1615) 15.3 (32/209) 20.5 (8/39) 5.3 (1/19)
Miscarriage rate in % (n)
e
23.3 (129/554) 33.3 (16/48) 20.0 (2/10) 0 (0/1)
LBR when 1±4 eggs collected in % (n)
e
10.5 (26/248) 8.5 (7/82) 19.0 (4/17) 9.1 (1/11)
Cumulative LBR after three cycles 51.2% 38.9% 36.1% 19.2%
a
Signi®cant statistical comparison using c
2
cross-tabulation test with P < 0.001.
b
Values are not statistically signi®cant.
c
Number of ampoules = in cases of pure FSH (75 IU FSH) and in cases of HMG (75 IU FSH and 75 IU LH).
d
Signi®cant statistical comparison using ANOVA test with P < 0.001.
e
Not statistically signi®cant.
f
Mean no. of fertilized oocytes/mean no. of oocytes collected 3 100.
g
Mean of average amount of gonadotrophin used for stimulation.
H.Abdalla and M.Y.Thum
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patients taking FSH) of HCG were administrated. Oocytes were
aspirated using transvaginal ultrasound guidance 34±36 h after HCG
administration. 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 transfer of embryos.
De®nition of outcome
A mature follicle was de®ned as a follicle >17 mm on transvaginal
ultrasound scan. A miscarriage or spontaneous abortion was de®ned as
a pregnancy lost before 24 weeks of gestation. A pregnancy was
de®ned as a positive serum or urine HCG test and a sac seen on
ultrasound scan, or an ectopic pregnancy. A live birth was de®ned as a
pregnancy resulting in delivery of a viable infant. Twins and triplets
were counted as one live birth. Fertilization rate was de®ned as
number of two pronuclear (2 PN) embryos per number of oocytes
collected 3 100 for each treatment cycle including ICSI cycles.
Cancellation was de®ned as cycle started but no egg collection
performed. Treatment cycles which proceeded to egg collection but
with no eggs retrieved were included as normal cycles.
Data analysis
Data were collected in the Medical System for IVF (MedicalSys,
London, UK) and analysed with the Statistics Package for Social
Sciences (SPSS, Surrey, UK). Descriptive statistical analysis was
performed initially to examine the normality distribution of all
continuous variances for parametric statistical tests. Associations
between FSH values and pregnancy rates, miscarriage rates and live
birth rates (LBRs) were examined with a c
2
cross-tabulation test
strati®ed by age. Analysis of variance (ANOVA) was then conducted
to assess the relationships between FSH levels and 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
signi®cance was set at P < 0.05.
Results
Between January 1997 and December 2001, 2057 patients
underwent 3401 consecutive IVF/ICSI cycles. Analysis, how-
ever, was only performed. Analyses, however, was only
performed on the ®rst treatment cycle of each patient. Thus
only 2057 cycles are studied. We have analysed the data in
relation to different levels of FSH and found no difference in
pregnancy rate and LBR or other outcome parameters in
patients with FSH <5 IU/l, those between 5 and 8 IU/l and those
between 8 and 10 IU/l. We did, however, observe a signi®cant
changes if the value of FSH was >10 IU/l. All patients with FSH
<10 IU/l were therefore united in one group. For the purpose of
analysis, the cohort was thereafter divided into four groups as
follows: group A, FSH <10 IU/l; group B, FSH 10.1±15 IU/l;
group C, FSH 15.1±20 IU/l; and group D, FSH >20 IU/l.
Table I shows the patients' demographics, stimulation
characteristics and treatment outcome in all four cohorts.
Women's mean age was slightly higher in the higher FSH
groups but the difference was not statistically signi®cant. The
pregnancy rate and LBR per started cycle and per egg
collection were signi®cantly lower (P < 0.001) in the higher
FSH groups. There were no signi®cant differences between the
four groups with regard to duration of infertility, miscarriage
rate, fertilization rate, serum estradiol per follicle, duration of
stimulation and average number of embryos transferred.
Furthermore, the mean estradiol level was not different
between study groups. However, the amount of gonadotrophin
required to achieve follicular maturity and the average daily
dose of gonadotrophin used for stimulation were higher in the
elevated FSH groups. The average number of oocytes collected
and average number of available embryos for transfer were
signi®cantly reduced (P < 0.001) in the elevated FSH groups.
The cancellation rate was signi®cantly higher (P < 0.001) in the
elevated FSH groups. The highest FSH level measured in a
patient achieving a live birth was 32.8 IU/l. A singleton was
delivered at 39 weeks. We further analysed the cumulative
LBR after three cycles for each study group. This showed the
same pattern, with a reduction in cumulative LBR as the level
of FSH is elevated (group A = 51.2%, group B = 38.9%, group
C = 36.1% and group D = 19.2%).
Tables II and III examine the relationship between age and
level of FSH. Table II illustrates the effect of the level of FSH
in women below and above the age of 38. In this context, the
same trend as shown in Table I is apparent for the two age
groups; however, in those patients aged <38, the pregnancy
rate and LBR were reduced, but not signi®cantly, as FSH levels
increased. An LBR of at least 20% was always achieved in
patients with FSH between 10 and 20 IU/l, and 16.7% in
patients with FSH >20 IU/l. The miscarriage rate and
fertilization rate were not in¯uenced by the increased FSH
levels. For those patients aged >38, the pregnancy rate and
LBR were signi®cantly reduced as FSH levels increased;
however, the fertilization rate was not in¯uenced by the
increased FSH levels. None of the patients with FSH >20 IU/l
achieved a pregnancy in their ®rst cycle; however, 16.7% (1/6)
had a live birth in their second treatment cycle.
Table III examines the same data but illustrates the effect of
age within each FSH group. As shown, age is a signi®cant
factor affecting treatment outcome. For those patients in the
same FSH group, there was a marked and signi®cant difference
in the two age groups, i.e <38 and >38, whereby the younger
patients had a lower cancellation rate, higher numbers of eggs
collected, more embryos available for transfer, higher preg-
nancy rate, LBR and lower miscarriage rate. It is noticeable,
however, that the fertilization rate was not signi®cantly
different within any of the age subgroups.
Table IV compares the outcome for younger patients with
high FSH and older patients with normal FSH. As shown, age
was the most signi®cant factor in in¯uencing the outcome.
Although younger patients with high FSH appeared to have a
lower number of oocytes collected and lower number of
available and transferred embryos, their pregnancy rate and
LBR were both signi®cantly higher than those of older women
with normal FSH.
Discussion
Most clinics use a basal day 3 FSH level as a screening tool to
assess the chance of one particular patient achieving a
pregnancy or a live birth with IVF treatment. This practice is
based on earlier studies showing that elevated day 3 FSH levels
Elevated basal FSH and ART outcome
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are associated with a reduced success rate of ART (Scott and
Hofmann, 1995; Balasch et al., 1996; Barnhart and Osherof,
1998). However, there is no clear-cut division between a
normal and an elevated FSH level (van Montfrans et al., 2000;
Esposito et al., 2002). It has been suggested that the reason that
clinics refuse to treat patients with elevated basal FSH is to
maintain the clinic's overall success rate or to improve their
position in the league tables (Sharif and Afnan, 2003).
Women with elevated FSH could be a heterogeneous group.
Some may have true reduced ovarian reserve, other cases may
be due to the presence of heterophylic antibodies. Finally, FSH
receptor polymorphism could also result in an elevated value in
patients with otherwise normal ovaries (Lambalk, 2003). In
this study, however, we con®rm that elevated day 3 FSH levels
in a previous cycle are associated with a reduction in the
overall LBR if compared with women with normal basal FSH
levels. Nevertheless, the LBR is reasonable, especially in
cycling women under the age of 38 with FSH between 10 and
20 IU/l where the chance of a live birth is at least 20%. This is
comparable with the national average LBR in the UK (HFEA
Patient Guide, 2001) in patients who are not considered by
most assessment to be average. In fact, two patients with FSH
Table II. Stimulation characteristics and cycle outcome of patients aged <38 and >38 in all four FSH groups
Age <38 years Age >38 years
FSH groups Group A Group B Group C Group D Group A Group B Group C Group D
No. of patients 1082 87 20 6 639 156 38 27
Cancellation rate (%)
a
3.9 11.5 20.0 66.7 9.7 15.4 39.5 37.0
Average no. of oocytes collected
b
11.0 7.29 5.7 3.0 7.83 4.67 2.64 2.41
Fertilization rate (%)
c,d
60.0 58.2 56.1 73.1 58.4 58.4 64.6 60.2
No. of embryos available for transfer
b
6.13 3.62 4.25 4.00 4.46 2.86 2.00 1.94
Average no of embryos transferred
d
2.24 1.87 1.94 1.67 2.13 1.80 1.42 0.95
Pregnancy rate per started cycle in % (n) 40.3
d
(434/1082)
29.9
d
(26/87)
25.0
d
(5/20)
16.7
d
(1/6)
18.8
a
(120/639)
14.1
a
(22/156)
13.1
a
(5/38)
0.0
a
(0/27)
LBR per started cycle in % (n) 32.2
d
(348/1082)
21.8
d
(19/87)
20.0
d
(4/20)
16.7
d
(1/6)
12.1
a
(77/639)
8.3
a
(13/156)
10.5
a
(4/38)
0.0
a
(0/27)
Pregnancy rate per egg collection in % (n) 41.5
c
(434/1035)
33.8
d
(26/77)
31.3
d
(5/11)
50.0
d
(1/2)
20.8
a
(120/577)
16.7
a
(22/132)
21.7
a
(5/23)
0.0
a
(0/27)
LBR per egg collection in % (n) 33.6
d
(348/1035)
24.7
d
(19/77)
25.0
d
(4/16)
50.0
d
(1/2)
13.2
a
(77/577)
9.8
a
(13/132)
17.4
a
(4/23)
0.0
a
(0/27)
Miscarriage rate (%)
a
19.8 26.9 20.0 0 35.8 40.9 20.0 NA
Cumulative LBR after three cycles 62.1% 51.7% 37.8% 16.7% 33.1% 29.5% 32.9% 16.7%
a
Signi®cant statistical comparison using c
2
cross-tabulation test with P < 0.001.
b
Signi®cant statistical comparison using ANOVA test with P < 0.001.
c
Mean no. of fertilized oocytes/mean no. of oocytes collected 3 100.
d
Not statistically signi®cant.
Table III. Stimulation characteristics and cycle outcome of patients <38 and >38 years in all four FSH groups
Group A (FSH
<10.1 IU/l)
Group B (FSH
10.1±15 IU/l
Group C (FSH
15.1±20 IU/l)
Group D (FSH
>20 IU/ol)
<38 >38 <38 >38 <38 >38 <38 >38
No. of patients 1082 639 87 156 20 38 6 27
Cancellation rate (%)
a
3.9 9.7 11.5 15.4 20.0 39.5 66.7 37.0
Average no. of oocytes collected
b
11.0 7.83 7.29 4.67 5.7 2.64 3.0 2.41
Fertilization rate (%)
c,d
60.0 58.4 58.2 58.4 56.1 64.6 73.1 60.2
Available no of embryos for transfer
b
6.13 4.46 3.62 2.86 4.25 2.00 4.00 1.94
Average no of embryos transferred
d
2.24 2.13 1.87 1.80 1.94 1.42 1.67 0.95
Pregnancy rate per started cycle in % (n) 40.3
(434/1082)
18.8
(120/639)
29.9
d
(26/87)
14.1
a
(22/156)
25.0
d
(5/20)
13.1
a
(5/38)
16.7
d
(1/6)
0.0
a
(0/27)
LBR per started cycle in % (n) 32.2
(348/1082)
12.1
(77/639)
21.8
d
(19/87)
8.3
a
(13/156)
20.0
d
(4/20)
10.5
a
(4/38)
16.7
d
(1/6)
0.0
a
(0/27)
Pregnancy rate per egg collection in % (n) 41.5
(434/1035)
20.8
(120/577)
33.8
d
(26/77)
16.7a
(22/132)
31.3
d
(5/11)
21.7
a
(5/23)
50.0
d
(1/2)
0.0
a
(0/27)
LBR per egg collection in % (n) 33.6
(348/1035)
13.2
(77/577)
24.7
d
(19/77)
9.8
a
(13/132)
25.0
d
(4/16)
17.4
a
(4/23)
50.0
d
(1/2)
0.0
a
(0/27)
Miscarriage rate (%)
a
19.8 35.8 26.9 40.9 20.0 20.0 0 NA
Cumulative LBR after three cycles 62.1% 33.1% 51.7 29.5% 37.8% 32.9% 16.7% 16.7%
a
Signi®cant statistical comparison using c
2
cross-tabulation test with P < 0.001.
b
Signi®cant statistical comparison using ANOVA test with P < 0.001.
c
Mean no. of fertilized oocytes/mean no. of oocytes collected 3 100.
d
Not statistically signi®cant.
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>20 IU/l achieved a live birth, one in her ®rst cycle and the
other in her second cycle, giving a cumulative LBR of 19.2%.
Indeed, in patients of all groups of elevated levels of FSH
(>10 IU/l) where the age was <38, the LBR was in excess of
20% per single cycle, with a cumulative LBR after three cycles
of 49.3%. This, we believe, is a far better choice for a
signi®cant number of women than the alternatives of oocyte
donation and adoption.
In this study, there was no attempt to check the level of FSH
in the treatment cycle itself. Previous studies (Scott et al.,
1990; Martin et al., 1996) have demonstrated that inter-cycle
variability in basal FSH values did not predict changes in
ovarian response to gonadotrophin stimulation and thus may
not be used to select an optimal cycle in which to stimulate an
individual patient. These studies also reported that one
previous elevated day 3 FSH determination dramatically
decreased the chance of future IVF-ET pregnancy.
El-Toukhy et al. (2002) argued that young age does not
protect against the adverse effects of reduced ovarian reserve,
suggesting that an elevated day 3 basal FSH level is not only
associated with low response, but also with poor quality
oocytes. They in fact argued that patients with elevated day 3
FSH perform as badly as much older patients with normal FSH.
This was not the case in this study. We have shown that
although younger cycling patients with high FSH had signi®-
cantly lower number of oocytes collected and a lower number
of available and transferred embryos, their pregnancy rate and
LBR were signi®cantly higher and their miscarriage rate was
signi®cantly lower than older women with normal FSH. Their
study was, however, a mixture of two groups, those with
elevated day 3 FSH and also those with a previous poor
response to stimulation and, therefore, the conclusions cannot
be made (and should not have been) speci®c to patients with a
high basal FSH level. Furthermore, the mean FSH value in all
three age groups in their study was <10 IU/l.
Cycling women with elevated FSH required more ampoules
for stimulation; this could be due to a true poor response or a
possible bias due to knowledge in advance of a basal FSH value
encouraging the clinician to prescribe a higher dose of
gonadotrophins. The fact, however, is that regardless of the
increasing dose of gonadotrophins, there was a higher cancel-
lation rate and the ultimate number of eggs collected was
progressively reduced in the elevated FSH groups. The
fertilization rate, however, was the same in all groups,
indicating that oocyte quality is not affected by the basal
FSH level. This ®nding is in keeping with the ®ndings of Sharif
et al. (1998). Overall, however, the number of embryos
available for transfer was lower for those patients with a high
basal FSH, and thus the number of embryos to choose from and
the number of embryos transferred were lower in that group.
This resulted in a lower pregnancy rate. This implies that
elevated basal FSH is associated with low ovarian reserve, but
is not synonymous with poor oocyte quality. This ®nding is
illustrated in several other studies (Check et al., 2002; Esposito
et al., 2002; van Rooij et al., 2003).
It is of interest to note that the fertilization rate was affected
neither by the level of FSH nor the age of the women. The
miscarriage rate, however, was affected by age but not by the
FSH level. Within the same age group, it was shown that the
miscarriage rate does not increase with an increase in basal
FSH level; however, the miscarriage rate does signi®cantly
increase with increased age. The increased miscarriage rate is
therefore associated with age-related changes in the structure
of the chromosomes of the oocytes. Furthermore, high FSH
therefore does not re¯ect ageing oocytes, it is just that fewer are
produced. This ®nding contradicts that of El-Toukhy et al.
(2002) who showed that poor responders have a high miscar-
riage rate regardless of age. However, they did not compare the
miscarriage rate with a normal control group. In addition, as
mentioned above, their population was a mixture of patients
Table IV. Stimulation characteristics and cycle outcome of patients <38 and FSH >10 IU/l versus patients >38 years and FSH <10 IU/l
Age <38 and
FSH >10 IU/l
Age >38 and
FSH <10 IU/l
P-value
No. of patients) 113 639
Mean age 6 SD 33.5 6 3.0 40.57 6 2.2
Duration of infertility (mean 6 SD) 4.43 6 3.2 5.31 6 4.6 NS
Cancellation rate (%) 15.9 9.7 0.039
Days of taking gonadotrophins (mean 6 SD) 12.5 6 3.5 11.3 6 2.5 NS
No of ampoules
a
consumed (mean 6 SD) 46.0 6 17.6 44.0 6 16.1 NS
Estradiol (IU) per follicle on HCG day 336.82 460.46 0.184
Average no. of oocytes collected (mean 6 SD) 6.77 6 6.11 7.83 6 5.49 0.069
Fertilization rate (%)
c
58.1 58.4 NS
Average no. of embryos available for transfer 3.73 4.46 NS
Average no. of embryos transferred 1.88 2.13 NS
Pregnancy rate per started cycle in % (n) 28.3 (32/113) 18.8 (120/639) 0.016
LBR per started cycle in % (n) 21.2 (24/113) 12.1 (77/639) 0.008
Pregnancy rate per egg collection in % (n) 33.7 (32/95) 20.8 (120/577) 0.004
LBR per egg collection in % (n) 25.3 (24/95) 13.2 (77/577) 0.003
Miscarriage rate (%) 25.0 35.8 0.173
Cumulative LBR after three cycles 49.3% 33.1%
a
Number of ampoules = in cases of pure FSH (75 IU FSH) and in cases of HMG (75 IU FSH and 75 IU LH).
NS = difference not statistically signi®cant (P > 0.05).
Elevated basal FSH and ART outcome
897
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with high FSH as well as poor responders with a normal FSH.
Nasseri et al. (1999) found an increased incidence of abnormal
karyotype in the abortuses of patients with elevated FSH and/or
estradiol. We have no data regarding the karyotype of the
abortuses, but the miscarriage rate was no different between the
different levels of FSH within the same age group.
Furthermore, they did not ®nd a signi®cant difference in the
incidence of abnormal karyotype in women aged <35 years.
From the data in this study, we can conclude that an elevated
basal FSH level does not indicate deterioration of oocyte and
embryo quality. The fertilization rate does not decrease and the
miscarriage rate is not increased. Our ®nding implies that the
reduction in pregnancy rate is a result of a reduced number of
oocytes collected and subsequently the limited choice of
embryos available to be transferred. This was clearly demon-
strated in cycles in which only 1±4 eggs were collected. In
those patients, there was no signi®cant difference in the LBR
between all FSH groups. This further con®rms that the
observed reduction in LBR in the overall data was due to
lower quantity of eggs rather than poor quality of these eggs. In
other words, patients assume an LBR related to their age and
the number of eggs they produce rather than the level of FSH.
Clinicians should therefore advise patients with a high basal
FSH level to expect a lower pregnancy rate, due to the fewer
eggs they will produce, as compared with their counterparts of
similar age who produce a higher number of eggs. Clinicians
and patients alike should therefore accept that patients with a
high FSH level will have poorer ovarian response and be
prepared to go ahead and undergo egg collection when a small
number of follicles has developed.
In summary, cycling women with high basal day 3 FSH will
have a lower chance of achieving a live birth, but there is still a
reasonable chance of success even with FSH levels up to 20 IU/
l. In the current system, many women with elevated FSH are
led to believe that they are unsuitable for IVF treatment and
would have no chance of a successful outcome. Therefore,
these women are forced to consider other treatment options to
provide them with the chance of motherhood, although not
with their own genetic child. For these women, a chance,
although a reduced one of achieving a pregnancy with their
own genetic child is a precious and important opportunity for
them to consider. Some woman may feel that a lower chance is
better than no chance at all. The level of basal FSH should not
be used as a screening tool to select patients for treatment;
instead it should be used as additional information to counsel
patients appropriately regarding the realistic chance of con-
ception as well as aiding the clinician in determining the
appropriate dose of gonadotrophins.
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Submitted on August 26, 2003; resubmitted on November 24, 2003;
accepted on November 26, 2003
H.Abdalla and M.Y.Thum
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... On the other hand, although circulating bFSH levels have classically been used to predict the fertility potential, clinical practice has revealed a limited usefulness and lack of precision (Fridén et al., 2011;Brugo Olmedo et al., 2013). The levels of bFSH were negatively correlated to the number of oocytes retrieved (Lee et al., 2009;Pinto et al., 2009;Abdalla & Thum, 2004;Li et al., 2016;Daney de Marcillac et al., 2017). Low serum levels of bFSH were associated to higher mean number of high quality embryos (Pinto et al., 2009), and higher FR (Jawed et al., 2016), pregnancy rates (Abdalla & Thum, 2004;Pinto et al., 2009;Sahin et al., 2021) and LBR (Abdalla & Thum, 2004;Sahin et al., 2021). ...
... The levels of bFSH were negatively correlated to the number of oocytes retrieved (Lee et al., 2009;Pinto et al., 2009;Abdalla & Thum, 2004;Li et al., 2016;Daney de Marcillac et al., 2017). Low serum levels of bFSH were associated to higher mean number of high quality embryos (Pinto et al., 2009), and higher FR (Jawed et al., 2016), pregnancy rates (Abdalla & Thum, 2004;Pinto et al., 2009;Sahin et al., 2021) and LBR (Abdalla & Thum, 2004;Sahin et al., 2021). ...
... The levels of bFSH were negatively correlated to the number of oocytes retrieved (Lee et al., 2009;Pinto et al., 2009;Abdalla & Thum, 2004;Li et al., 2016;Daney de Marcillac et al., 2017). Low serum levels of bFSH were associated to higher mean number of high quality embryos (Pinto et al., 2009), and higher FR (Jawed et al., 2016), pregnancy rates (Abdalla & Thum, 2004;Pinto et al., 2009;Sahin et al., 2021) and LBR (Abdalla & Thum, 2004;Sahin et al., 2021). ...
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... However, it is possible in some patients that DOR and POI occur within a spectrum, as they share many etiologies and features [4,15,16]. With increasing age, the proband may finally be diagnosed with POI because the AMH value was only 0.37 ng/mL and one follicle in each ovary at her age of 24. ...
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... Generally, women with high levels of blood FSH on day 2 or 3 of the menstrual cycle have a smaller chance of having a live baby than other women of the same age, even with ovulation induction and IVF (37). Abdalla and Thum (38) studied all patients who were candidates for IVF/ICSI treatment between January 1997 and December 2001 in Lister hospital, London. Patients were divided into four groups by FSH level. ...
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... FSH was another significant predictor of the success of infertility treatments. Previous studies indicated that although the cut-off of 10 IU/ml for this factor led to the highest CPR and live birth for IVF treatment, no significant association was found between pregnancy and FSH levels 37 . In another study, there was a significant association between CPR and FSH values 9 IU/L or higher in IUI treatment 38 . ...
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... The elevated basal FSH in many women discourage the option of ICSI/IVF as treatment option for them. This is due to that the high basal FSH is associated with lower assisted reproduction treatment results (16) . The age and elevated serum level of basal FSH in women are used as predictive criteria associated with diminished fertility (17) .In this study we re-evaluated the association between the ICSI outcome and the maternal age and basal FSH level. ...
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Serum vascular endothelial growth factor (VEGF) is involved in follicular vascularization, oxygenation, and consequently in oocyte maturation and embryo development. Unanswered questions remain regarding the relationship of intrafollicular VEGF level in preovulatory leading follicles to oocyte maturation and ovarian reserve during ovarian stimulation. We conducted this study to investigate the relationship of intrafollicular VEGF level in the fluid of single preovulatory leading follicles to ovarian reserve and oocyte maturation in patients receiving GnRH antagonist in vitro fertilization (IVF) protocol treatment. One hundred and eighty-five patients receiving IVF treatment were recruited and assigned to low-, normal-, and high-ovarian-reserve groups according to their serum anti-Müllerian hormone (AMH) level. Follicular fluid (FF) in preovulatory leading follicles, serum profiles, and clinical variables were collected for analysis. The result disclosed a significant among-group difference in FF VEGF concentration. Moreover, the serum AMH level was also negatively correlated with FF VEGF level. The oocyte maturation rate tended to be increased at higher AMH levels. FF VEGF concentration was significantly positively correlated with basal FSH level. In conclusion, FF VEGF concentration has a negative association with ovarian reserve level and oocyte maturation rate in patients undergoing GnRH antagonist IVF protocols.
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Diminished ovarian reserve (DOR) is one of the primary causes of poor ICSI outcomes. Therefore, this study was performed to speculate which of the following parameters: AMH, AFC, and women’s age can be used as a predictor factor of the DOR in women aged < 40 years. This prospective study enrolled 500 women suffering from idiopathic infertility problems and who underwent GnRH antagonist multiple-dose stimulation protocol. The women were divided into two groups: normal fertility (FSH ≤ 10 mIU/mL, n = 300) and DOR (FSH > 10 mIU/mL, n = 200). At the time of the study, the average of women age was 29.3 ± 5.7 years. A significant reduction was found in AMH level, AFC, number of mature, immature oocytes, fertilized oocytes, embryos transferred, and β-hCG level in the DOR group compared to the normal fertility group (P < 0.001). Conversely, a significant increase was shown in the age of the DOR group compared to the normal fertility group (30.8 ± 5.8 vs. 28.2 ± 5.4, respectively; P < 0.001). A significant negative association was found between the AFC, the number of mature oocytes, fertilized oocytes, embryos transferred, and the basal level of FSH in the DOR group (P < 0.01). The receiver operating characteristics (ROC) demonstrated that AMH level and AFC had the highest accuracy, followed by age in the prediction of DOR (P < 0.001) with a cut-off value of ≤ 1.2 ng/mL, ≤ 4.5, and > 29.5 years, respectively. This study exhibited that the levels of AMH and AFC are the best biomarkers, followed by age for the prediction of DOR in women < 40 years old. Furthermore, AMH is the only independent factor that is significantly related to DOR in women.
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High FSH doses during superovulation of heifers with a small ovarian reserve increase the number of dysfunctional ovulatory-size follicles that do not ovulate in response to human chorionic gonadotropin (hCG). Thus, anti-Müllerian hormone (AMH) and antral follicle count (AFC), two well-established biomarkers of responsiveness of individuals to superovulation, are hypothesized to be positively linked to number of dysfunctional ovulatory-size follicles developing in response to superovulation with high FSH doses. To test this hypothesis, heifers with a small ovarian reserve were stimulated beginning on Day 1 of the estrous cycle with twice daily treatments for 4 days with each of four Folltropin-V (FSH) doses (35 IU, 70 IU (industry standard), 140 IU, or 210 IU) followed by prostaglandin F2α to regress corpora lutea (CL) from the previous estrous cycle and hCG to induce ovulation. Ovulatory-size follicles were classified as functional or dysfunctional based on whether they ovulated and formed CL in response to hCG. FSH dose did not impact the relationship between AMH, AFC and the number of functional or dysfunctional ovulatory-size follicles developing in response to superovulation. Thus, data from the four superovulations were averaged for each heifer. AMH and AFC were positively associated with the subsequent number of functional and dysfunctional ovulatory-size follicles and the proportion of ovulatory-size follicles that are dysfunctional after superovulation. Because measurements of AMH concentration and AFC predict the number but not functionality of ovulatory-size follicles, which may also impact oocyte quality, these ovarian reserve biomarkers are concluded to be unlikely useful to improve IVF or embryo transfer outcomes in heifers with a small ovarian reserve.
Article
OBJETIVO: Determinar el punto de corte de la concentración basal de FSH y su valor pronóstico en la obtención de ovocitos con protocolo de antagonistas en ciclos de fertilización in vitro. MATERIALES Y MÉTODOS: Estudio retrospectivo, efectuado en pacientes en el primer ciclo de fertilización in vitro con un protocolo antagonista. Se formaron dos grupos de acuerdo con las concentraciones basales de FSH: en el grupo 1 permanecieron las pacientes con concentración de FSH menor de 7 mIU/mL y en el grupo 2 con concentraciones mayores de 7 mIU/mL. Parámetros de estudio: dosis total de gonadotropinas, pico de estradiol, cantidad de ovocitos recuperados, de ovocitos en metafase II, de embriones disponibles para transferencia y tasa de embarazo. Para comparar las diferencias de medias entre ambos grupos se realizó la prueba de t de Student. El análisis estadístico se realizó con el programa JMP 9.0. El valor de p < 0.05 se consideró estadísticamente significativo. RESULTADOS: Se registraron 1441 pacientes: 927 en el grupo 1 y 514 en el grupo 2. Las mujeres del grupo 1 reportaron menor edad (34.3 vs 35.3; p < 0.05), mayor cantidad de ovocitos (11.15 vs 8.26; p < 0.05) y, en general, ovocitos maduros (7.4 vs 5.3; p < 0.05). No se encontró diferencia significativa en las tasas de embarazo entre ambos grupos (27.98 vs 28.92; p = 0.54). CONCLUSIONES: La concentración basal de FSH mayor de 7 mIU/mL se correlaciona significativamente con menor cantidad de ovocitos recuperados en los ciclos de fertilización in vitro con protocolo de antagonistas.
Article
Objective: To investigate whether IVF outcome of patients older than 40 years of age with basal FSH levels less than 15 IU/L differs from that in patients 40 years of age or younger with basal FSH levels of 15 IU/L or greater. Design: Prospective observational study. Setting: Tertiary academic fertility center. Patient(s): Women 41 years of age or older with basal FSH levels less than 15 IU/L (n = 50), and women 40 years of age or younger with elevated basal FSH levels (n = 36) undergoing their first IVF cycle. Intervention(s): IVF treatment using a long suppression protocol with recombinant FSH at a fixed starting dose of 150 IU/L. Main Outcome Measure(s): Ovarian response, ongoing pregnancy rates, and implantation rates. Result(s): The high FSH group experienced more cycle cancellations due to absent follicular growth than did the high age group (31% vs. 8%). However, the high FSH group had better implantation rates per embryo (34% vs. 11%), higher ongoing rates per ET (40% vs. 13%), and higher ongoing pregnancy rates per cycle (25% vs. 10%). In both groups, poor responders had lower pregnancy rates. Conclusion(s): The outcome of IVF differs between patients older than 40 years of age with normal FSH levels and relatively young patients with elevated FSH levels. This finding may have implications for the management of these patients.
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
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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
Expression of the positively acting 5S gene-specific transcription factor, TFIIIA, is regulated during development, with highest levels of mRNA and protein occurring during oogenesis. By analysis of TFIIIA promoter mutants microinjected into late stage Xenopus oocytes, we have determined DNA sequences required for the transcription of this gene and we have identified proteins that bind to these regulatory sequences. A negative element lies between positions -306 and -289. Three positive-acting sequences are located between positions -289 and -253, -250 and -173, and -144 and -101. Gel shift analyses of TFIIIA promoter fragments incubated with Xenopus oocyte extracts have identified two DNA-protein complexes. One complex, designated B1, requires sequences within the promoter region extending from -271 to -253 while the second complex, designated B2, involves promoter sequences from -235 to -221. The protein involved in formation of the B1 complex has been found to be related to the human adenovirus major late transcription factor, USF.
Article
The purpose of this study was to determine whether basal or stimulated (or both) serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on day 3 of the cycle before administration of exogenous gonadotropins can predict stimulation response and in vitro fertilization (IVF) outcome. Eighty consecutive new patients underwent a gonadotropin-releasing hormone (GnRH) stimulation test on the morning of cycle day 3. All patients underwent the same stimulation protocol consisting of a combination of FSH and human menopausal gonadotropin (hMG). Paired discriminant analysis of FSH0 (at 0 minutes from GnRH injection) and LH0 revealed seven distinct groups of patients with statistically significant differences among the means: groups 1, 2, and 3 (26.25%) with higher means FSH0:LH0; group 4 (40%) with mean FSH0:LH0 (both levels less than 10 mIU/ml) of 1:1, and groups 5, 6, and 7 (33.75%) with higher mean LH0:FSH0. Canonical discriminant analysis of both basal and stimulated serum FSH and LH levels confirmed the seven groups and did not add to the information from analysis of FSH0 and LH0 only. Serum estradiol (E2) response during stimulation, as well as the number of preovulatory oocytes aspirated and transferred, was highest in the groups with a higher mean LH0:FSH0, intermediate in the group with mean FSH0:LH0 of 1:1, and lowest in the group with a higher mean FSH0:LH0. No pregnancy occurred in the higher FSH:LH groups. It is concluded that basal serum gonadotropin levels can distinguish different populations of IVF patients who tend to behave differently in terms of E2 response, oocytes obtained and transferred, and pregnancy rates and outcome.
Article
Gonadotropin secretion during the post-menopausal period is considerably higher than during the reproductive years. In this study, we present evidence that changes in the hypothalamic-pituitary-ovarian unit occur over a period of years before the onset of menstrual irregularity which heralds the menopause. FSH and LH were measured in blood samples taken on 6 days during the mid-follicular phase from 127 regularly cycling women aged between 23 and 49 yr. The women aged 23-30 yr were taken as the control group and the remainder were grouped in 2-yr age bands. A significant increase in FSH underwent a further increase in the oldest group (48-49 yr) in whom LH also became significantly elevated. The difference in the timing of the change in FSH and LH concentrations was related not only to chronological age but also to the number of years before the menopause. The increase in FSH occurred 5-6 yr pre-menopause, that in LH not until 3-4 yr before the cessation of menstruation. It is concluded that an early sign of the aging of the reproductive mechanism can be detected in women who are having normal ovulatory cycles. The regulation of FSH and LH secretion appears to be sufficiently independent to permit the observed differences in the age of onset of these premenopausal increases.
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 determine the IVF-ET pregnancy potential of women with variably elevated day 3 FSH. Cohort evaluation of 1,868 consecutive IVF-ET cycles January 1991 to December 1994. University hospital infertility unit. Four cohorts of couples were defined based on day 3 FSH determinations with an arbitrary threshold of 20 mIU/mL, only > or = 20 mIU/mL, always < 20 mIU/mL, current < 20 mIU/mL but one previous > or = 20 mIU/mL, and current < 20 mIU/mL but two or more previous > or = 20 mIU/mL (conversion factor to SI unit, 1.00). In vitro fertilization-embryo transfer. Fetal heart activity on luteal day 40 transvaginal ultrasound. No pregnancies occurred in 53 cycles with day 3 FSH only > or = 20 mIU/mL. In 1,750 women whose day 3 FSH levels were always < 20 mIU/mL, the pregnancy rate (PR) per cycle was 16.5%. In 54 cycles in which day 3 FSH was > or = 20 one time only, but < 20 mIU/mL during the treatment cycle, the PR was 5.6%. In 11 cycles where two or more previous FSH determinations were > or = 20 mIU/mL but with a current day 3 FSH < 20 mIU/mL, no pregnancies occurred. Our data leads us to the conclusion that day 3 FSH determination precede every IVF cycle and that cycles with FSH > or = 20 mIU/mL be canceled. It also suggests that women with two previous elevations of day 3 FSH be discouraged from future IVF cycles. The 5.6% pregnancy per cycle with one previously elevated FSH warrants extreme pessimism in discussion of further cycles.