ArticlePDF Available

Elevated basal FSH and embryo quality: Lessons from extended culture embryos : RSH and blastocyst quality

Authors:

Abstract and Figures

The relationship between elevated basal FSH and embryo quality remains a topic of heated discussion among practitioners of ART. Some authors suggest a negative effect of raised FSH on the quality of embryos and therefore on IVF treatment outcome. We postulate that women with elevated FSH who respond well to ovarian stimulation and have embryos to transfer, have the same chance of conceiving like women of a similar age with normal FSH. To test this hypothesis, we studied women with elevated basal FSH who made enough embryos to qualify for blastocyst culture and day 5 embryo transfer. Analysis of data collected prospectively, on women age 25-43 years, who underwent IVF between January 2005 and December 2006. The women were divided into: those with high FSH (> or = 10 IU/L) and women with normal FSH (<10 IU/L). We analysed data to show treatment outcome in the two groups, following embryo transfer on day 3 and after transfer on day 5. Outcome measures include number of oocytes retrieved, number of embryos available, implantation rate, pregnancy and live birth rate. Among the 1,858 women who under-went a day 3 transfer, 1,368 had basal FSH < or = 10 IU/L, and in 492 basal FSH was above 10 IU/L. The average number of oocytes retrieved was lower among women with elevated FSH (10.12 +/- 5.6 Vs 6.16 +/- 3.9). Women with a normal FSH, had a higher pregnant and live birth rate than those with elevated FSH (43.3% vs 27.9% p = 0.021) and (30.8% vs 17.6% p = 0.028) respectively. 398 women made enough embryos to qualify for extended embryo culture to blastocysts. Of these 366 had an FSH < or = 10 IU/L and 32 had FSH > 10 IU/L. In this group, there was no significant difference in the pregnancy and live birth rates between women with elevated and those with normal FSH, (67.2% vs 65.6%) and (51.9% vs 43.8%) respectively. In this selected group of women where quantity is not an issue, the quality of embryos was same irrespective of whether the basal FSH was low or high. Women with elevated basal FSH who respond well to stimulation and generate a good number of oocytes / embryos have a chance of becoming pregnant and having a live birth similar to that of women of their age. Women should therefore not be denied the benefits of IVF based solely on the basal FSH level as a subset may respond well and therefore have a good chance of taking home a baby.
Content may be subject to copyright.
ASSISTED REPRODUCTION
Elevated basal FSH and embryo quality: lessons
from extended culture embryos
Raised FSH and blastocyst quality
MY Thum &E Kalu &H Abdalla
Received: 12 October 2008 / Accepted: 18 May 2009 / Published online: 10 June 2009
#Springer Science + Business Media, LLC 2009
Abstract
Background The relationship between elevated basal FSH
and embryo quality remains a topic of heated discussion
among practitioners of ART. Some authors suggest a
negative effect of raised FSH on the quality of embryos
and therefore on IVF treatment outcome. We postulate that
women with elevated FSH who respond well to ovarian
stimulation and have embryos to transfer, have the same
chance of conceiving like women of a similar age with
normal FSH. To test this hypothesis, we studied women
with elevated basal FSH who made enough embryos to
qualify for blastocyst culture and day 5 embryo transfer.
Methods Analysis of data collected prospectively, on
women age 2543 years, who underwent IVF between
January 2005 and December 2006. The women were
divided into: those with high FSH (10 IU/L) and women
with normal FSH (<10 IU/L). We analysed data to show
treatment outcome in the two groups, following embryo
transfer on day3 and after transfer on day 5. Outcome
measures include number of oocytes retrieved, number of
embryos available, implantation rate, pregnancy and live
birth rate.
Results Among the 1,858 women who under-went a day 3
transfer, 1,368 had basal FSH10 IU/L, and in 492 basal
FSH was above 10 IU/L. The average number of oocytes
retrieved was lower among women with elevated FSH
(10.12±5.6 Vs 6.16± 3.9). Women with a normal FSH, had
a higher pregnant and live birth rate than those with
elevated FSH (43.3% vs 27.9% p= 0.021) and (30.8% vs
17.6% p=0.028) respectively. 398 women made enough
embryos to qualify for extended embryo culture to
blastocysts. Of these 366 had an FSH 10 IU/L and 32
had FSH>10 IU/L. In this group, there was no significant
difference in the pregnancy and live birth rates between
women with elevated and those with normal FSH, (67.2%
vs 65.6%) and (51.9% vs 43.8%) respectively. In this
selected group of women where quantity is not an issue, the
quality of embryos was same irrespective of whether the
basal FSH was low or high.
Conclusion Women with elevated basal FSH who respond
well to stimulation and generate a good number of oocytes /
embryos have a chance of becoming pregnant and having a
live birth similar to that of women of their age. Women
should therefore not be denied the benefits of IVF based
solely on the basal FSH level as a subset may respond well
and therefore have a good chance of taking home a baby.
Keywords Basal FSH,IVF .Embryo quality .Blastocysts
Introduction
The inverse relationship between elevated early follicular
phase follicle stimulating hormone (FSH) and diminished
ovarian reserve is universally accepted. However the link
between a raised FSH and quality of the resultant embryos
remains a topic of heated discussion among practitioners of
ART. Various authors have suggested a negative effect of
elevated FSH on embryonic quality and outcome of IVF
[1-3]. Others including papers from our unit, have argued
that elevated basal FSH reflects a quantitative rather than
qualitative declined of ovarian function [4]. In our previous
J Assist Reprod Genet (2009) 26:313318
DOI 10.1007/s10815-009-9313-y
M. Thum (*):H. Abdalla
Lister Fertility Clinic, Lister Hospital,
Chelsea Bridge Road,
London SW1W 8RH, UK
e-mail: mythum@doctors.net.uk
E. Kalu
Assisted Conception Unit, Kingston Hospital NHS Trust,
Galsworthy Road,
Kingston Upon Thames KT2 7 QB, UK
e-mail: ekalu@doctors.org.uk
paper [4] we showed that the lower pregnancy and live
birth rates among women with elevated basal FSH was due
to the fewer number of oocytes produced rather than the
quality of the oocytes. We postulated that if a patient with
elevated FSH gets to the stage of egg collection and embryo
transfer, their chance of becoming pregnant and having a
live birth was similar to that of women of their own age,
with a similar number of embryos generated. To test this
hypothesis further, we studied women with elevated basal
FSH, who under went extended embryo culture to
blastocyst and day5 embryo transfer. In our unit, only
women who have 6 or more embryos on day 3, with at least
3 at 8-cell stage are offered extended embryo culture.
Hence all women with elevated basal FSH who had
blastocyst transfer had enough embryos on day 3 to have
been eligible for extended culture. Based on our hypothesis,
we expect that there will be no significant difference in the
pregnancy and live birth rate following blastocyst transfer
among women with elevated and those with normal basal
FSH, if there is no significant difference in the number of
available embryos in the two groups.
Materials and methods
We prospectively collect and store data of all patients
undergoing IVF/ICSI in our unit in a Medical System for
IVF (MedicalSys, London, UK). We analysed data on all
women aged 25 to 43 years who underwent IVF/ICSI
treatment cycles with known basal FSH level in the two
years between January 2005 and December 2006. The basal
FSH level had been checked prior to commencing treatment.
The women were divided into two groups: those with a high
basal FSH (10 IU/L) and women with a low basal FSH
(<10 IU/L). The level of 10 IU/L was found to be the level
above which there was a significant change in the pregnancy
rate in our previous study [4]. We then analysed data to
show treatment outcome in the two groups, following
embryo transfer on day2 or 3 and following extended
embryo culture and transfer on day 5. Outcome measures
include, number of oocytes retrieved, number of embryos
available, implantation rate, pregnancy and live birth rate.
FSH assay
Serum FSH was measured in early follicular phase (days 2 to
4) in the cycle preceding treatment. FSH concentration was
measured using a two-step chemiluminescent microparticle
immunoassay (CMIA) and analysed by Abbott Architect
System (Abbott Laboratories IL). The analytical sensitivity
of the assay was calculated to be better than 0.05 mlU/ml (n =
36 runs). Analytical sensitivity is defined is defined as the
concentration at 2 SDs from the ARCHITECT FSH Master-
Check Level 0 (0.00 mlU/ml), and represent the lowest
measurable concentration of FSH that can be distinguished
from zero. The specificity 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-assay coefficients
of variation were 2.9 and 3.8% respectively.
IVF stimulation and blastocyst culture
In brief, the IVF treatment protocol includes ovarian
stimulation, with either recombinant FSH, human meno-
pausal gonadotrophin or urinary FSH. A trans-vaginal scan
was performed prior to ovarian stimulation to ensure the
ovaries were quiescent.
Patients were down regulated with either Nafarelin or
Buserelin at mid luteal phase. When follicles reached pre-
ovulatory size (18 to 22 mm), 10,000 IU of hCG was
administrated. Oocytes were aspirated using trans-vaginal
ultrasound guidance 34 to 36 h after hCG administration. For
fertilisation, standard insemination or ICSI was performed as
clinically appropriate. Embryo culture was performed using
a sequential micro-drop system at an atmosphere of 56%
CO
2
at 37°C. SAGE sequential cleavage media (SAGE In-
vitro Fertilization Inc. Trumbull, Connecticut) was used for
embryos on day13, and patients who met the criteria for
extended culture continued to the blastocyst stage. To
qualify for extended culture patients should have at least 6
embryos on day3, with at least 3 at 8-cell stage and at top
quality [5]. If this condition was met, all embryos were
allowed to progress to the blastocyst stage irrespective of
their cell number or quality. Quinns Advantage Fertiliza-
tion medium (SAGE In-vitro Fertilization Inc. Trumbull,
Connecticut) was used for day35 embryos. Using the
Gardner and Schoolcraft scoring system [5], the best quality
blastocysts were selected on day 5 for transfer. 400 mg
cyclogest pessary was administered to all the patients for
luteal support. A pregnancy test was performed 10 days
following blastocyst transfer and a transvaginal ultrasound
scan at 56 weeks to determine the number of gestation. In
this study a pregnancy was defined as a positive serum or
urine HCG test and a sac on ultrasound scan, or an ectopic
pregnancy. A live birth was defined as a pregnancy
resulting in a viable infant. Twins were counted as one live
birth. Fertilisation rate was defined as number of two
pronuclear (2PN) embryos per number of oocytes collected
x 100 for each treatment cycle including ICSI cycles.
Data analysis
Data was collected in Medical System for IVF (MedicalSys,
London, UK) and analysed by Statistics Package for Social
314 J Assist Reprod Genet (2009) 26:313318
Sciences (SPSS, Surrey, UK). Descriptive statistical analysis
was performed initially to examine the normal distribution
of all continuous variances for parametric statistical tests.
Chi-square Cross Tabulation test was used to analyse the
significant difference in pregnancy rates, live birth rates and
twin rate between the groups. Statistical significant was set at
P<0.05.
Results
Two thousand two hundred fifty six cycles of IVF/ICSI in
women with known basal FSH levels during study period
were identified. 1,858 women had day 2/3 embryo transfer,
while 398 women had extended embryo culture to
blastocysts; transferred on day 5.
Day2 or 3 embryo transfer (n=1858)
Among the 1858 women who under-went a day 2 or 3
transfer, 1368 had a basal FSH10 IU/L, and in 492
women the basal FSH was above 10 IU/L. The average
number of oocyte retrieved was significantly lower among
women with elevated FSH (10.12 ±5.6 Vs 6.16±3.9)
compared to women with FSH below 10 IU/L. In the low
FSH group, 594 of 1368 (43.3%) women got pregnant and
421 had a live birth (30.8%) compared to 138 of 494
(27.9%) and 87 (17.6%) respectively among women with
elevated basal FSH (Table 1).
Day5 embryo (blastocyst) transfer (n=398)
Among the women who under went blastocyst transfer, 366
women had a basal FSH10 IU/L and in 32 women the
basal FSH was greater than 10 IU/L. In this group, 246 of
366 (67.2%) women with low FSH got pregnant and 190
(51.9%) had a live birth. 21 of 32 (65.6%) women with
elevated FSH got pregnant and 14 (43.8%) had a live birth.
(Table 2).
Table 3shows the outcome when women with similar
basal FSH level (and who generated enough embryos for
blastocyst culture) were sub-divided according to age.
Among the 366 women with low FSH, 240 were age
<38, and 126 were38 years old. 149 of 240 (70.8%)
women age <38 with low FSH got pregnant. In this sub-
group, the implantation rate was 57.5% and 57.1% (137/
240) had a live birth. The results were better than that
obtained by their older counter parts with similar FSH
levels (Table 3). In this older group of women age38, with
low FSH, 61 of 126 (48.4%) got pregnant. The implanta-
FSH10IU/L FSH> 10IU/L P-value
Number of patients 1368 494 NA
Basal FSH levels IU/L ± SD 6.82± 1.7 15.79± 6.1 NA
Mean age ± SD 37.1± 4.5 38.9± 3.8 NS
Days of taking Gonadotrophins (mean ± SD) 11.5± 3.1 11.9± 3.8 NS
No of ampoules
a
consumed (mean ± SD) 38.6 ± 15.6 47.4 ±18.7 0.011
Average no. of oocytes collected ± SD 10.12± 5.6 6.18± 3.9 0.019
Average no of normal fertilized embryos ± SD 6.18± 3.9 3.40± 2.5 0.001
Average no of embryos transferred ± SD 1.92± 0.58 1.88 ± 0.62 NS
Pregnancy rate (%) 43.3% (594/1368) 27.9% (138/494) 0.021
Live birth rate (%) 30.8% (421/1368) 17.6% (87/494) 0.028
Table 1 Treatment outcome in
high or low basal FSH groups
for women age43 following
day2 or 3 embryo transfer
NS difference not statistically
significant (P> 0.05); NA not
applicable; aeach ampoules
contain 75 iu of gonadotrophins
FSH10IU/L FSH>10IU/L P-value
Number of patients 366 32 NA
Basal FSH levels IU/L ± SD 7.11± 2.1 13.21 ± 3.8 NA
Mean age ± SD 35.4± 4.7 36.8 ± 5.9 NS
Days of taking Gonadotrophins (mean ± SD) 10.9± 2.8 11.8 ±3.9 NS
No of ampoules
a
consumed (mean ± SD) 39.2± 11.7 49.2± 19.7 0.019
Average no. of oocytes collected ± SD 12.7 ±5.2 9.87±3.1 0.046
Average no of normal fertilized embryos ± SD 8.8±3.8 7.5± 2.9 NS
Average no of embryos transferred ± SD 1.62± 0.21 1.66± 0.29 NS
Pregnancy rate (%) 67.2% (246/366) 65.6% (21/32) NS
Live birth rate (%) 51.9% (190/366) 43.8% (14/32) NS
Table 2 Treatment outcome in
high or low basal FSH groups
for women age43 following
blastocyst transfer
NS difference not statistically
significant (P> 0.05); NA not
applicable; aeach ampoules
contain 75 iu of gonadotrophins
J Assist Reprod Genet (2009) 26:313318 315
tion rate in this subgroup was 41.2% and 42.1% (53/126)
had a live birth (Table 3).
Of the 32 women with elevated basal FSH, 18 were age
<38, and 14 were age38. 12 of 18 (66.7%) women < 38
got pregnant. The implantation rate in this subgroup was
45.2% and 61.1% (11/18) had a live birth. Among the 14
women38 who had elevated FSH, 3 got pregnant
(21.4%). The implantation rate was 22.7% and 21.4% had
a live birth (3/14) (Table 3).
Table 4shows the results when women of similar ages
where categorized according to basal FSH levels. Of the
258 women age<38, 240 had a basal FSH10 IU/L and in
18 women the basal FSH was>10. The implantation rate,
pregnancy rate and live-birth rate was similar between
women with normal and those with elevated basal FSH
(57.5 vs 45.2%, 70.8 vs 72.2%, and 57.1 vs 61.1%
respectively).
Of the 140 age38, 126 had a basal FSH10 IU/L and
in 14, the FSH was > 10 IU/L. Again the implantation rate,
pregnancy and live-birth rates was not statistically different
between women with normal FSH and those with elevated
FSH (41.2 vs 22.7%, 60.3 vs 57.1% and 42.1 vs 21.4%
respectively) (Table 4).
Discussion
The assumption that an elevated basal FSH is associated
with adverse IVF outcome has been used to counsel women
against proceeding with IVF treatment using their own
gametes. This practice has significant implications, not only
in this era of donor scarcity, but also as it deprives these
women of the opportunity of having their own biological
off-springs. This assumption has also been instrumental in
the formulation of health authority criteria for state funded
IVF treatment. Some Primary care Trusts in the UK, would
not fund treatment for women with basal FSH over 10 IU/L
since the outcome is expected to be poor.
We have shown that elevated basal FSH is not
necessarily associated with poor IVF outcome. It is
generally agreed that elevated FSH is associated with
diminished ovarian reserve [6]. Our data is in keeping with
Table 3 Treatment outcome for women with blastocyst transfer in cycles with high or low basal FSH level stratified according to age
Low FSH High FSH
Age< 38 Age 38 PAge<38 Age 38 P
Number of patients 240 126 NA 18 14 NA
Mean age ± SD 33.1 ± 3.3 39.9± 4.1 NA 34.8± 4.2 39.5±4.4 NA
Basal FSH levels IU/L ± SD 6.8±2.3 7.7±2.8 NA 12.4 ±2.6 14.3± 2.6 NA
No. of oocytes collected ± SD 12.7±6.6 12.6 ±5.1 NS 10.5 ± 2.6 9.1±3.4 NS
No of embryos transferred ± SD 1.52± 0.2 1.81±0.6 NS 1.72± 0.33 1.57 ±0.69 NS
Pregnancy rate (%) 170/240 (70.8%) 76/126 (60.3%) 0.028 13/18 (72.2%) 8/14 (57.1%) 0.032
Implantation rate (%) 210/365 (57.5%) 94/228 (41.2%) 0.009 14/31 (45.2%) 5/22 (22.7%) 0.005
Live birth rate (%) 137/240 (57.1%) 53/126 (42.1%) 0.007 11/18 (61.1%) 3/14 (21.4%) 0.028
NS difference not statistically significant (P>0.05); NA not applicable
Table 4 Treatment outcome for women with blastocyst transfer in cycle with young or older age women and high or low basal FSH groups
Age< 38 Age 38
Low FSH High FSH PLow FSH High FSH P
Number of patients 240 18 NA 126 14 NA
Mean age ± SD 33.1± 3.3 34.8± 4.2 NA 39.9± 4.1 39.5 ±4.4 NA
Basal FSH levels IU/L ± SD 6.8± 2.3 12.4 ± 2.6 NA 7.7 ± 2.8 14.3 ± 2.6 NA
No. of oocytes collected ± SD 12.7± 6.6 10.5± 2.6 NS 12.6± 5.1 9.1 ±3.4 NS
No. of embryos transferred ± D 1.52±0.2 1.72 ±0.33 NS 1.81± 0.6 1.57 ± 0.69 NS
Implantation rate (%) 210/365 (57.5%) 14/31 (45.2) 0.126 94/228 (41.2%) 5/22 (22.7%) 0.065
Pregnancy rate (%) 70.8% (170/240) 72.2% (13/18) 0.57 60.3% (76/126) 57.1% (8/14) 0.516
Live birth rate (%) 57.1% (137/240) 61.1% (11/18) 0.47 42.1% (53/126) 21.4% (3/14) 0.101
NS difference not statistically significant (P>0.05); NA not applicable
316 J Assist Reprod Genet (2009) 26:313318
this observation, as women with elevated FSH were shown
to have a lower egg yield compared to those with a normal
FSH (Table 1). This reduced number of oocytes translates
to fewer numbers of embryos available for transfer and this
we believe is responsible for the lower pregnancy and live
birth rates in women with elevated FSH.
Our results on women who responded well to controlled
ovarian hyperstimulation despite an elevated basal FSH
clearly show that treatment outcome is similar to their
counterparts with normal basal FSH (Table 2). Age is
clearly the most important factor that determines outcome
of treatment and this reflects on the results on Table 3,
where among women with similar FSH levels, younger
women consistently did better than their older counter-part.
When we nullified the effect of age by analyzing women in
similar age groups, the results for women with elevated
FSH was comparable to their peers with normal FSH. We
have shown that some women with elevated FSH can still
respond well to stimulation and make blastocysts. And
when this happens, their chances of taking home a baby is
similar to those of women of their own age, with a similar
number of embryos generated. Our results are in keeping
with others [7-9] who also showed that women with
elevated basal FSH levels can still achieve reasonable
pregnancy rates with ART. Women with elevated FSH may
be a heterogenous group. Some may have true reduced
ovarian reserve, and therefore respond poorly to ovarian
stimulation. Other cases of elevated FSH may be due to the
presence of heterophylic antibodies. Furthermore FSH
receptor polymorphism could also result in an elevated
value in women with otherwise normal ovaries [10]. This
latter group of women are likely to respond well to
stimulation if given the opportunity to under go IVF.
In our series, women with elevated basal FSH who made
enough oocytes and embryos to meet our criteria for blastocyst
culture had a pregnancy rate of 65.6% and a live birth rate of
43.8% which was comparable to 67.2% and 51.9% respec-
tively achieved by their counterparts with normal FSH. As it is
currently not possible to identify this subset of women with
high egg /embryo yielddespite elevated FSH, denying some
women the opportunity to under go IVF on the sole basis of
FSH levels, may be difficult to justify.
This is the first paper to discuss blastocyst culture among
women with elevated FSH and to establish that women
with elevated basal FSH also have the potential to develop
good quality blastocysts. Embryo quality is generally
reflected by implantation rates. That women with elevated
basal FSH had the same implantation rates as their age-
matched peers implies that embryo quality is not signifi-
cantly affected by FSH level. It seems that maternal age
rather than basal FSH is a better determinant of embryonic
quality. The lower implantation rate, clinical pregnancy and
live birth rates among the older women in both the low and
high FSH groups may reflect age associated qualitative
decline of ovarian reserve, rather than an FSH effect as has
been suggested by some authors. [11,12]. The negative
effect of advance maternal age rather than basal FSH on
embryo quality has been assessed in a recent paper from
our unit. In that paper [13], we showed that although the
proportion of aneuploid embryos increased with advanced
maternal age, the percentage of aneuploid embryos was not
significantly different between women with high basal FSH
and those with normal FSH. Our results clearly confirms the
hypothesis that women with elevated basal FSH, who make
adequate number of embryos, have a chance of having a live-
birth similar to their peers with normal basal FSH.
Conclusion
While women with elevated FSH may be counselled to
expect a lower pregnancy rate following IVF, we have
shown that this is dependent on how well they respond to
ovarian stimulation. Women with elevated FSH who get to
the stage of egg collection and embryo transfer, have the
same chances of becoming pregnant and having a live birth
similar to that of women of their own age, with a similar
number of embryos generated. Pre-treatment management
of patientsexpectation is however important since out-
come is poorer among those with poor response to
controlled ovarian hyperstimulation. Women with elevated
basal FSH should however not be denied the benefits of
IVF based solely on FSH levels, as a subgroup of them
have a good chance of conceiving.
References
1. Scott RT Jr, Hofmann GE. Prognostic assessment of ovarian
reserve. Fertil Steril. 1995;63:111.
2. Balasch L, Creus M, Fabregues F, Carmona F, Casamitjana R,
Ascoso C, et al. Inhibin, follicle-stimulating hormone, and age as
predictors of ovarian response in in-vitro fertilisation cycles
stimulated with gonadotrophin-releasing hormone agonist-
gonadotrophin treatment. Am J Obstet Gynecol. 1996;175:1226
30. doi:10.1016/S0002-9378(96)70032-7.
3. Barnhart K, Osherof J. Follicle stimulating hormone as a predictor
of fertility. Curr Opin Obstet Gynecol. 1998;10:22732.
doi:10.1097/00001703-199806000-00009.
4. Abdalla H, Thum MY. An elevated basal FSH reflects a
quantitative rather than qualitative decline of the ovarian reserve.
Hum Reprod. 2004;19(4):8938. doi:10.1093/humrep/deh141.
5. Gardner DK, Schoolcraft WB. In vitro culture of human blasto-
cysts. In: Jansen R, editor. Towards reproductive certainty: fertility
and genetics beyond 1999. Canforth (UK): Parthenon; 1999.
6. Lenton EA, Sexton L, Lee S, Cooe ID. Progressive changes in LH
and FSH and LH:FSHratio in women throughout reproductive life.
Maturitas. 1988;10:3543. doi:10.1016/0378-5122(88)90129-6.
7. Levi AJ, Raynault MF, Bergh PA, Drews MR, Miller BT, Sctt RT.
Reproductive outcome in patients with diminished ovarian
J Assist Reprod Genet (2009) 26:313318 317
reserve. Fertil Steril. 2001;76:6669. doi:10.1016/S0015-0282
(01)02017-9.
8. Esposito MA, Coutifaris C, Barnhart KT. A moderately elevated
day3 FSH concentration has limited predictive value, especially in
younger women. Hum Reprod. 2002;17:11823. doi:10.1093/
humrep/17.1.118.
9. van Rooij IAJ, Bansi L, Broekmans FJM, Looman C, Habbema J,
te Velde ER. Women older than 40 years of age and those with
elevated follicle-stimulating hormone levels differ in poor re-
sponse rate and embryo quality in in vitro fertilisation. Fertil
Steril. 2003;79:4828. doi:10.1016/S0015-0282(02)04839-2.
10. Lambalk CB. Value of elevated follicle-stimulating hormone
levels and the differential diagnosis during the diagnostic
subfertility work-up. Fertil Steril. 2003;79:48990. doi:10.1016/
S0015-0282(02)04841-0.
11. El-Toukhy T, Khalaf Y, Hart R, Taylor A, Braude P. Young age
does not protect against the adverse effects of reduced ovarian
reservean eight year study. Hum Reprod. 2002;17:151924.
doi:10.1093/humrep/17.6.1519.
12. Toner JP, Philput CB, Jones GS, Muasher SJ. Basal follicle
stimulating hormone level is a batter predictor of in vitro
fertilisation performance than age. Fertil Steril. 1991;55:78991.
13. Thum MY, Abdalla H, Taylor D. Relationship between women's
age and basal follicle-stimulating hormone levels with aneuploidy
risk in in vitro fertilization treatment. Fertil Steril. 2007;2007
(Oct):20. Epub ahead of print.
318 J Assist Reprod Genet (2009) 26:313318
... Decreased ovarian reserve is a rather common problem among subfertile women, with approximately 31% of ART cycles using fresh non-donor eggs or embryos reported by the Society of Assisted Reproductive Technology being complicated by a diminished ovarian reserve in 2015 (8). The inverse relationship between elevated early follicular phase FSH and the diminished ovarian reserve is universally accepted (9). Several studies demonstrated that high day-3 basal concentrations of FSH are associated with a low response to ovarian stimulation, high cancellation rates, and a low chance of success in patients undergoing ART treatment (4,5,10 However, the link between elevated FSH values and quality of the resultant embryos is a matter of debate, unlike the decreased number of oocytes retrieved. ...
... Another study by the same group also showed that women with elevated serum FSH levels had lower numbers of oocytes retrieved and lower clinical pregnancy rates compared to women with FSH levels in the normal range. However, women with an elevated basal FSH level who responded well to gonadotropin stimulation and generated a good number of oocytes/embryos had similar chances of becoming pregnant and having a live birth as women in the same age range with normal levels of FSH (9). The results of our study also demonstrated comparable clinical pregnancy rates per ET among the four groups, despite the retrieval of a decreasing number of retrieved oocytes with increasing FSH values, which was in line with the above-mentioned studies. ...
Article
Full-text available
p> OBJECTIVE: Despite the availability of better biomarkers, basal day 3 follicle-stimulating hormone is widely available and often used as the first-line test in ovarian reserve evaluation. The aim of this study was to evaluate the outcomes of cycles with elevated (>12 IU/mL) basal follicle-stimulating hormone values. STUDY DESIGN: Cycles with basal day 3 follicle-stimulating hormone values >12 IU/mL were divided into four cohorts according to follicle-stimulating hormone levels: group I, follicle-stimulating hormone between 12-15 IU/m, group II between 15-20 IU/mL, group III between 20-25 IU/mL and group IV >25 IU/mL. Both demographic characteristics and controlled ovarian stimulation parameters were retrospectively reviewed. RESULTS: Total antral follicle count was significantly higher in group I compared to the other three groups (p=0.001). Number of follicles ≥17 mm on human chorionic gonadotropin (hCG) day, number of retrieved oocytes, mature oocytes and fertilized oocytes were significantly higher in group I compared to the other groups (p=0.003, p=0.001, p=0.001, and p=0.001, respectively). No significant difference was found between groups regarding cancellation rates. The rate of embryo transfer per started cycle was significantly higher in group I compared to group III and group IV (p=0.001). Clinical pregnancy rates per embryo transfer were comparable among the groups. CONCLUSION: Despite the retrieval of lower quantities of oocytes, reasonable pregnancy rates could be achieved if embryo transfer was performed in cycles with follicle-stimulating hormone values over 12 IU/mL.</p
... These include BMI, age, hormone levels, follicular count and semen characteristics. [10][11][12][13][14] Age and BMI have shown to interfere with the regular menstrual cycle and hormone regulation in females. High FSH levels have shown an association with increased pregnancy rates. ...
... High FSH levels have shown an association with increased pregnancy rates. 11 These characteristics are important to analyze as they predict positive outcomes early in the treatment cycle. ...
... Several studies suggest a negative effect of raised FSH on the quality of embryos and in vitro fertilization (IVF) treatment outcome [11][12][13]. Women with an elevated basal FSH indicate diminished ovarian reserve and reduced numbers of oocytes and embryos [14,15]. Therefore, we speculate that the reason might be related to FSH regulating the immune function of DMSCs. ...
Article
Full-text available
Objective Women with an elevated basal FSH indicate diminished ovarian reserve and reduced oocyte and embryo numbers. DMSCs are likely to be involved in immune tolerance of pregnancy maintenance. We investigate the effect of follicle-stimulating hormones on the immunomodulatory functions of DMSCs. Methods DMSCs were primary cultured from decidual tissue. Pretreated DMSCs with mitomycin C, combined with CD4 ⁺ T lymphocytes, DMSCs + CD4 ⁺ T co-culture system was established. Different physiological dose FSH (3 ng/ml,10 ng/ml,30 ng/ml,100 ng/ml) were used to co-culture system. Cytokines (IFN-γ, IL-2, IL-4, IL-6, IL-10, TNF-α) and other proteins (FSHR, MyD88) were measured. Results Compared with the control group (FSH (0 ng/mL) + CD4 ⁺ T + DMSCs), the FSH concentration was 10, 30, and 100 ng/ml, IL-6 levels were significantly reduced ( P < 0.05). IL-6, MyD88 protein expression was remarkably decreased ( P < 0.05). Conclusion FSH/FSHR could negatively regulate the immunosuppressive function of DMSCs by reducing secretion of IL-6 levels through MyD88 pathways, but upstream and downstream signalling pathways require further validation.
... The fact that none of the aforementioned parameters was observed to be indicative of the fertilization or cleavage rate is in accordance to literature. It has been observed that AFC, E 2 , AMH, FSH or LH should not be employed as predictive factors regarding either fertilization or cleavage rate 44,[47][48][49][50] . Only prolactin levels have been reported in literature to be predictive of fertilization and cleavage rate, with a cut-off value of 16.05 ng/ mL 50 . ...
Article
Full-text available
The aim of this study is the development of a prediction model indicating successful application of Oocyte Retrieval performed during the Luteal Phase (LuPOR) in poor responders, as defined by the retrieval of at least one MII oocyte. Recruitment included 1688 poor responders diagnosed as per Bologna Criteria, undergoing natural cycle ICSI between 2012 and 2020. Oocyte collections were performed during the follicular phase and during the luteal phase similarly. Antral Follicle Count (AFC), Estradiol (E2) levels evaluated on both trigger days prior to Follicular Phase Oocyte Retrieval (FoPOR) and LuPOR, and the number of small follicles 8–12 mm that were not aspirated during FoPOR were identified as predictive factors indicative of an efficient LuPOR practice with an Area Under the Curve (AUC) of 0.86, 0.86, 0.89 as well as 0.82 respectively. The combination of the above-mentioned characteristics into a prediction model provided an AUC of 0.88, specificity and a sensitivity of 0.73 and 0.94 respectively and an accuracy of 0.89. The model provided a positive predictive value (PPV) of 93.5% and a negative predictive value (NPV) of 46.8%. The clinical conclusion of the present study aims to be of added value to the clinician, by providing a prediction model defining the POR population benefiting from LuPOR. The high PPV of this model may renders this tool helpful for the practitioner that considers LuPOR.
... Many factors are related to decreased ovarian reserve (DOR) that includes age, ovarian surgery, endometriosis, chemotherapy, and abdominal radiation [5,6] . Generally, an early follicular phase serum FSH concentration > 10 IU/L indicates an increased risk of DOR [7][8][9] . The basal FSH value, defined as the serum level during the first 2-3 days of the menstrual cycle, can be used for screening, counselling and other diagnostic purposes. ...
... According to a study conducted by Islam et al, FSH and ovarian volume do not correlate with the ovarian response 16 whereas Thum et al. concluded that women with high basal FSH respond well to stimulation and produce good number of oocytes giving them an equal chance to become pregnant as compared to normal women of their age. 17 Antral follicles are measured by the means of TVS. AFC of 8-10 is considered as a predictor of normal response whereas more than 14 considered as a good predictor of hyper response. ...
Article
Full-text available
Objective: To determine the ovarian reserve parameters in patients presenting for IVF and intracytoplasmic sperm injection (ICSI) treatment and its association with the number of follicles retrieved and number of oocyte retrieved and fertilized. Methods: A retrospective cross sectional study was conducted at Australian Concept Infertility Medical Centre from January 2017 to August 2017. Around 120 couples presenting to infertility clinics selected for IVF and ICSI with Females (25-45) had their FSH, AMH and AFC done. After ovulation induction, its response was determined by number of follicles retrieved, quality of oocytes retrieved or fertilized and inseminated. SPSS version 20 was used for the purpose of data analysis. Results: The median age of the patients was 34 (29-38) years. A moderate negative correlation of age and FSH levels was observed with quality of oocytes, Number of oocyte inseminated, number of oocyte fertilized and number of follicle restored. However, a positive correlation of AMH and AFC levels were found with quality of oocytes, Number of oocyte inseminated, number of oocyte fertilized and number of follicle restored. The correlation of AMH levels with number of oocyte inseminated (rho 0.729, p-value <0.001), number of oocyte fertilized (rho 0.721, <0.001) and number of follicle restored (rho 0.723, p-value <0.001) were found strongly correlated. Conclusion: Our study concluded that AMH and AFC have a strong correlation with number of follicles restored and number of oocytes retrieved whereas FSH and age has a weak correlation with the number of follicles restored and number of oocytes retrieved.
Article
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.
Article
Objective To estimate the aneuploidy rates in young women with diminished ovarian reserve (DOR) before treatment and poor ovarian response (POR) postretrieval. Design Retrospective cohort study. Setting A single academically-affiliated fertility clinic. Patient(s) Autologous frozen embryo transfer cycles from December 2014 to June 2020 were reviewed. Demographic and clinical factors that impact outcomes were used for propensity score matching (PSM) in a ratio of 2:1 and 4:1 for preimplantation genetic testing for aneuploidy pre-cycle DOR and POR after stimulation, respectively. Intervention(s) None. Main Outcome Measure(s) Aneuploid rates, defined as the number of aneuploid blastocysts divided by the number of biopsied blastocysts per cycle. No euploid embryos to transfer, defined as all cohorts of embryos being aneuploid. Result(s) A total of 383 women diagnosed with DOR were compared with matched controls. Aneuploid rates did not differ significantly between the two groups (42.2% vs. 41.7%; RR = 1.06; 95% CI, 0.95–1.06). No differences were identified in live birth rates per transfer between women with and without DOR after euploid single-embryo transfers (56.0% and 60.5%, respectively). An additional PSM analysis to assess aneuploidy rates for patients with POR (<5 oocytes) vs. those without it, resulted in similar rates of aneuploidy between the two comparison groups (41.1% vs. 44%, R = 1.02; 95% CI, 0.91–1.14). The prevalence of cycles with “no euploid embryos” in the POR cohort was higher (26% vs. 13%); however, rates of cases with a single embryo available for biopsy were lower in the DOR group, relative to controls (11% vs. 31%). Conclusion(s) Young women diagnosed with DOR or POR exhibited equivalent aneuploidy rates and live birth rates per euploid embryo transfer in a large matched population, based on age, body mass index, and IVF cycle initiation. The lower percentage of cycles with no euploid embryo available for transfer in DOR and POR patients is because of the decreased total number of oocytes/developing embryos and not because of increased aneuploidy rates in these groups.
Article
The assessments of oocyte quality and quantity and endocrine profile have traditionally been the cornerstone of the general workup of couples with infertility. Over the years, several clinical, hormonal, and functional biomarkers have been adopted to assess ovarian function and identify endocrine disorders before assisted reproductive technology. Furthermore, the genetic workup of patients has drastically changed, introducing novel markers. This not only allowed the prediction of response to ovarian stimulation but also contributed toward the development of a safer and more efficient management of women undergoing assisted reproductive technology. The scope of this review is to provide an overview of the current and novel strategies adopted for the assessment of ovarian function and ovulatory and endocrine disorders in women planning to conceive. Furthermore, it aims to provide an insight in the role of novel genetic biomarkers and use of expanded carrier screening as part of preliminary workup of women with infertility.
Article
Full-text available
Objective: The present study aimed to evaluate reproductive outcomes and determine the predictors of clinical pregnancy and live birth in women with elevated baseline follicle-stimulating hormone (FSH) levels, who have undergone intracytoplasmic sperm injection (ICSI) treatment. Methods: This retrospective study included 1011 ICSI cycles of women with high baseline FSH levels (> 10 IU/L), from a tertiary university IVF center between 2010 and 2015. Logistic regression analysis was performed to evaluate the prognostic factors of clinical pregnancy and live birth. Results: Among the 1011 ICSI cycles, the clinical pregnancy and live birth rates per oocyte retrieval were 19.5% and 14.3%, respectively. The live birth rates were 21.1% and 1.7% in women aged ≤30 years and those aged ≥40 years, respectively. In addition, the live birth rate was 1.47-fold higher in women from whom >3 oocytes were retrieved, compared to those from whom ≤3 oocytes were retrieved (p=0.047). Logistic regression analysis indicated that the age categories ≤30y, 36-39y and ≥40y, level of baseline FSH (≥20 IU/L) and the ovarian response (≤3 or >3 oocytes retrieved) were significantly associated with live birth. Conclusions: Our study indicated that age, baseline FSH level, and ovarian response are independent predictive factors for clinical pregnancy and live birth among women with baseline FSH levels >10 IU/L.
Article
Full-text available
Ovarian reserve significantly influences IVF outcome. Low response to ovarian stimulation due to reduction of ovarian reserve is occasionally encountered in young women. The aim of this study was to evaluate the outcome of IVF treatment in young patients with reduced ovarian reserve. Between January 1993-2001, 762 consecutive patients satisfied the definition of reduced ovarian reserve (raised early follicular phase FSH or gonadotrophin stimulation cycles where three or fewer oocytes were retrieved after routine FSH stimulation) and were included in the study. They were classified into three age groups: young (< or = 30 years), intermediate (31-38 years) and older (>38 years). The three age groups were similar with respect to basal (day 3) serum FSH and estradiol concentrations, cause of infertility and number of previous treatment cycles. Implantation (13, 9.6 and 9.8%), clinical pregnancy (11.8, 10.2 and 10%) and live birth (7.4, 7.3 and 6.8%) rates were not significantly different in the three age groups respectively (P > 0.05). This study shows that younger patients with reduced ovarian reserve have a poor outcome of IVF treatment similar to their older counterparts. Such information may be helpful in counselling these patients who otherwise might anticipate an outcome related to their chronological age.
Article
A study of 1,478 consecutive in vitro fertilization (IVF) cycles was made to determine if basal follicle-stimulating hormone (FSH) levels and age were independent predictors of IVF performance. Regression analyses indicated independent contributions of both basal FSH and age in predicting cancellation rate, peak estradiol, number of oocytes retrieved, fertilized, and transferred, and total and ongoing pregnancy rates. Miscarriage rate was unrelated to both age and basal FSH. Follicle-stimulating hormone level was a better predictor than age for all outcome variables examined and remained a significant predictor after accounting for age, etiology of infertility, and semen quality. The combined use of age and basal FSH in counseling patients improves the accuracy of prognosis, and may provide an index of functional ovarian reserve ("ovarian age").
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
A study of 1,478 consecutive in vitro fertilization (IVF) cycles was made to determine if basal follicle-stimulating hormone (FSH) levels and age were independent predictors of IVF performance. Regression analyses indicated independent contributions of both basal FSH and age in predicting cancellation rate, peak estradiol, number of oocytes retrieved, fertilized, and transferred, and total and ongoing pregnancy rates. Miscarriage rate was unrelated to both age and basal FSH. Follicle-stimulating hormone level was a better predictor than age for all outcome variables examined and remained a significant predictor after accounting for age, etiology of infertility, and semen quality. The combined use of age and basal FSH in counseling patients improves the accuracy of prognosis, and may provide an index of functional ovarian reserve ("ovarian age").
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
Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone (defined before treatment) and the woman's age both as single and combined predictors of ovarian response in an in vitro fertilization program where pituitary desensitization was routinely used. The study was a retrospective analytic investigation of 120 women undergoing the first cycle of in vitro fertilization. Forty consecutive cycles canceled because of poor follicular response were initially selected. As a control group, the nearest completed in vitro fertilization cycles before and after each canceled cycle (i.e., the closest cycles in temporal relationship to the index cycle) were used. The mean age and basal follicle-stimulating hormone level were significantly higher in the canceled than in the control group, whereas the basal inhibin level was significantly higher in the latter. Follicle-stimulating hormone and inhibin alone, with an accuracy (predictive value of ovarian response) of 70%, were better predictors of cancellation than age was. Any two or all three of these variables studied did not improve the predictive value of follicle-stimulating hormone or inhibin alone. Age is a poorer predictor than pretreatment basal follicle-stimulating hormone and inhibin levels for ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Basal follicle-stimulating hormone and inhibin have similar predictive properties and could therefore be used interchangeably.
Article
Tests for diminished ovarian reserve provide valuable prognostic information for women considering assisted reproductive technology. The best characterized screening tool for a general infertility patient is the clomiphene citrate challenge test. These screening tests do not have absolute sensitivity or specificity. Additionally, the predictive value of these tests can be low if used in a population at low risk. Patients with abnormal testing should be counselled that their chances of conception with assisted reproductive technology are poor. This may impact on the choice of aggressive treatment; however, the results of these tests should never be used to exclude patients from care.
Article
To compare reproductive outcome between women with normal ovarian reserve and women with abnormal ovarian reserve. Retrospective. Tertiary care center. Nine thousand eight hundred and two patients who had basal follicle-stimulating hormone (FSH) concentrations measured as part of an infertility evaluation. Monitoring of early pregnancy. Pregnancy loss rates, live birth rates. Of 1,034 patients with diminished ovarian reserve (DOR) (FSH > or =14.2 IU/L), 28 (2.7%) conceived. Twenty of these pregnancies (20/28; 71.4%) were lost in the first trimester. Pregnancy loss rates in women with DOR were 57.1% in women <35 years old, 63.5% in women 35-40 years old, and 90.0% in women >40 years old. These rates of pregnancy loss were significantly higher compared to age-matched patients with normal ovarian reserve. Women with DOR have exceedingly high rates of pregnancy loss, regardless of age. Women with diminished ovarian reserve should be counseled that, in addition to a low probability of conception, live birth rates are poor.
Article
A cycle day 3 FSH concentration is a popular screening tool for predicting success in achieving pregnancy after IVF. Difficulties interpreting this test have resulted from lack of consensus in defining an elevated FSH concentration, a change in the assays, and lack of controlling for factors which may confound the association between FSH concentration and pregnancy. Assessment was made of the ability of a moderately elevated (10-11.4 mIU/ml, World Health Organization 2nd International Standard (IRP 78/549) and elevated FSH (>11.4 mIU/ml, conversion factor to SI units, 1.00) in predicting ability to achieve pregnancy through IVF and embryo transfer, both independently, and after controlling for confounding variables such as age, diagnosis, and response to gonadotrophins. A total of 293 IVF cycles were retrospectively reviewed. An FSH (>11.4) was strongly associated with inability to achieve pregnancy after IVF both independently (P < 0.01) and after multivariate analysis (P < 0.01), and had a strong predictive value (100%). A moderately elevated FSH (10-11.4) was not statistically associated with pregnancy outcome either independently or after multivariate analysis, and had a low predictive value (71%). Much of the predictive value of an elevated FSH is confounded by poor response to gonadotrophin stimulation, which may be overcome in younger women.