Assessment of
ovulation
Aboubakr ElnasharBenha university Hospital, EgyptAboubakr Elnashar
CONTENTS
I. Physiology of ovulation
II. Methods of assessment of ovulation
III. LH urine test
IV. Uses of LH urine test
1.Timing of fruitful sexual intercourse
2.Timing of IUI
3.Timing of Post coital test
4.Contraception
5.Endometrial preparation for thawed embryo
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I. Physiology of Ovulation
Surge and peak?
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0 4 8 12 16 20 24 28
Key events in ovarian cycle
Menstruation
Day 1
Ovulation
Oestradiol
LH
1. Follicular growth
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0 4 8 12 16 20 24 28
LH surge
Menstruation
Day 1 Day 1
Days before Days after
Follicular phase Luteal phase
Ovulation
LH
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0 4 8 12 16 20 24 28
Menstruation
Day 1
Ovulation
Oestradiol
1. Follicular growth
LH
2. Ovulation
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0
What causes ovulation ?
4 8 12 16 20 24 28
What causes LH surge ?
Oestradiol
What effects does it have ?
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Hypothalamus
Pituitary
Ovary
GnRH
LHFSH
For most of the cycle negative feedback mechanism operates
-
Estradiol
↓ LH & FSHInhibited by estradiol
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Hypothalamus
Pituitary
Ovary
GnRH
But, with high level of estradiol maintained for long enough +
EstradiolLH surge
↑GnRH
↑Sensitivity to GnRH
+
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.
The cause of the LH surge
1. The negative feedback of E2 at the hypothalamic-pituitary
level turns to a positive feedback when E2 concentrations
reach a critical point.
2. The pituitary gland becomes highly sensitive to GnRH
stimulation, {increase of GnRH receptors}. Thus, the GnRH
surge produces the LH surge
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Normal serum values:FSH LH
Adult 5-10 mIU/ml 5-20 mIU/ml
Peak 2 times the basal level 3 times the basal level
Surge >25mIU/ml
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Follicular rupture occurs:
Positive LH urine test=
12 h after the surge (onset) of serum LH
around the point of LH peak.
Urine surge LH
Positive test
Serum LH
PeakSurge
24 H12 H36 H
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II. ASSESSMENT OF OVULATION
I. Symptoms:1. Mid cycle pain: Mittelschmerz
2. Mid-cycle bleeding
3. Thinning of cervical mucus
4. Regular cycle (variation no more than ±2 days)
5%: anovulatory
5% to 18.5%: anovulatory using urinary LH alone(Lynch et al, 2014)
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II. Tests:
1. BBT
Stressful
Predicted the day of ovulation in10% of cycles
Less accurate for confirming ovulation(Guermandi et al, 2001)
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2. Ultrasound folliculometry
Costly
Time consuming
To be reserved for induction ovulation or COS(NICE, 2013; Practice Committee of the ASRM, 2015; UpToDat,2016)
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Diagnosis of Spontaneous Ovulation
1. Mature F. (contain mature oocyte) = 17 – 25 mm (Inner dimensions)
2. Reduction in mature follicle size (40%) Or
Disappearance (60%)
3. Intra peritoneal fluid
-Normal: 1-3 ml
-With ovulation: 4- 5 ml
4. CL: 4-8 days after ovulation• Irregular thick wall .• Hypoechoic• May contain internal echos (hge.)• 15 mm
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3. Mid luteal serum progesterone
At D: -7
day 21: of a 28-day cycle
28: of 35
Reliable to confirm ovulation
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>3ng/mL is the most reliable evidence of recent
ovulation(NICE, 2013; Practice Committee of the ASRM, 2015; UpToDat,2016)
⩾5ng/ml confirms ovulation(Leiva et al, 2015)
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4. LH surge in urine
Advantages:
Quick
Sensitive
Inexpensive,
Pinpoint the day of ovulation
Reduced the uncertainty in interpretation
of progesterone levels by better-identifying
the time of peak progestrone secretion at
which to obtain serum
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LH urine tests
accurate and superior compared to •BBT charting
•Calendar calculation,
•Salivary ferning
•Vaginal or cervical discharge changes.(Owen, 2013)
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PMEB:
histologic dating is not a valid diagnostic method
lacks both accuracy and precision
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III. Urine LH test
A Semi-quantitative
test
Detects urinary LH
surge when serum
LH ≥ 25 mIU/ml
Accuracy: 96%
What?
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IV. Uses
1.Timing of fruitful sexual intercourse
2.Timing of IUI
3.Timing of Post coital test
4.Contraception
5.Endometrial preparation for thawed embryo
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1. Timing fruitful sexual intercourseSperms
Fertilizing capacity: 40-80 h,
Oocyte
life span: 12-24 h (Allen J. et al, 2000)
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The ‘‘Fertile window
Duration:
• Up to 6-days
• ±last between 1 day and 5 days
• Chance of pregnancy is significantly
greater the longer it lasts.
•when lasts for1 day: fecundability ratio is 0.11•when it lasts for 5 days: fecundability is 2.4 [6].
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Start:
•highly variable, unpredictable, even if cycles are usually
regular. (Wilcox et al, 2000)
•70%:
before day 10 or
after day 16 of their menstrual cycle
•Day 4 of the cycle: 2%
7 of the cycle: 17%
12 of the cycle: 54%
•Most women early in the cycle, although a
proportion do so much later, even past day 35.(Wilcox et al. 2000)
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End:
ending on the day of ovulation
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Determination:
• Tests to determine or predict the time of ovulation may
be useful.
(NICE, 2013; Practice Committee of the ASRM 2013)
• When to start the test?
When dominant follicle 15 mm:
daily urinary LH surge test to establish precise
ovulation timing: Perfect intercourse or IUI timing
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When to start the test?
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Optimal frequency and timing of intercourse
In follicular phase of the cycle:
every 2–3 days
At the predicted time of ovulation:
daily for 2–3 days
Abstinence until the day of ovulation can be
detrimental to sperm function.
No evidence that closely spaced ejaculations are
detrimental to fertility; in fact, the opposite applies in
some cases [7]
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Frequent intercourse (every 1 to 3 D) during the
fertile window yields the highest pregnancy rates
Intercourse on the day of the LH surge and the
following day, they may be missing three or four
fertile days before this time and thus reducing their
chance of conception.
Intercourse on the day after ovulation, the
probability of conception is zero
{short survival time of the oocyte
swift change in the nature of the cervical mucus}. (Dunson et al, 1999).
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Probability of conception
10%:
when intercourse occurred 5 days before
ovulation
33%:
when it took place on the day of ovulation
94% of pregnancies were attributed to sperm that
were 1 or 2 days old, Although sperm can retain their capacity to fertilise in vitro for 5 days, and they can survive in oestrogenised cervical mucus for 7 days.(Wilcox et al, 2000)
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Mistiming of intercourse
A cause for failure to conceive (Robinson &Ellis, 2007)
The use of LH urine testing:
•identifies fertile days: intercourse accordingly,
•should be considered for couples seeking to
conceive during the first year, before other
attempts at infertility diagnosis are made
Costs
Strain on the couple.
Accurate
Simple to use
Home based(May, 2000)
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Effect of LH urine testing on the level of stress(Tiplady et al, 2013)
No difference in levels of stress between women
using LH urine tests to time intercourse
compared with women who were trying to
conceive without any additional aids
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2. Timing of IUIMethods:
1. ultrasound monitoring of follicular growth
followed by the administration of hCG
2. Detection of urine LH surge
Reliable for the prediction of ovulation and
timing of IUI.(Martinez et al, 1992)
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How?
Follicular rupture occurs:
Positive urine test=
12 h after the surge (onset) of serum LH
around the point of LH peak.
If one adds a fertilizing life span for ovum of
only 12 h to be on the safe side: IUI 36 h after
positive urine test is very satisfactory.
Urine surge LH
Positive test
Serum LH
PeakSurge
24 H12 H36 H
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US and HCG injection Vs urine LH surge
No evidence of a difference in LBR [Cochrane SR, 2014].
Optimum time interval from HCG injection to IUI:
24 h to 48 h.
No difference in LBR
Choice should be based on
1. convenience for the patient, medical staff
2. costs and dropout levels
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Combine US and urine LH surge
US monitored IUI:
29% had a spontaneous LH surge before
ovulation triggering
decrease pregnancy rates (Antaki et al, 2011)
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IUI timing combining dominant
follicle diameter and LH testing(Antaki et al, 2011)
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3. Avoidance of pregnancyBy periodic abstinence.
(Brown et al, 1991)
LH urine results
To identify the ovulatory cycle and the day of
ovulation
Mean period of abstinence of 7 days:
•Gave 4 days or more warning of ovulation in 99%
of cycles
•allowed intercourse to be resumed 1 to 3 days
after ovulation in 88%,
No pregnancy occurred from intercourse during the
late safe days defined by the test
Some early day pregnancies occurred through long
sperm survivals of 6 to 8 daysAboubakr Elnashar
4. Timing of postcoital testUrinary LH TESTING
do not appear to improve timing of the postcoital
test as compared with traditional timing methods.(Corsan et al, 1993)
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5. Endometrial preparation in frozen thawed embryos
Cryopreservation of embryos
an integral part of ART programs.
Increased dramatically
1.Trend towards transferring fewer embryos after a fresh IVF cycle
2. Improved laboratory techniques(Skovmand 1997; Diniz, 2002; Fineschi et al., 2005; Gordts et al.,
2005; Thompson, 2005; Le Lannou et al., 2006; JOINT SOGC-CFAS, 2008; Min et al., 2010).
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Methods:Regular ovulatory Irregular or unovulatory
I. Natural II. Artificial=Hormone
replacement
III. Ovulation induction
True Modified E and P Gna, E and P GnT Letrozole Nolvadex
Functioning ovaries:•Any method
Quiescent Ovaries (e.g. donor oocyte recepient with
ovarian failure)•Only HRT with E and P
Many infertility units:•use a mixture of protocols for FET.
Best method:•Little agreement in ovulatory women (Ghobara and Vandekerckhove, 2008;Weissman et al., 2009).
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True Natural cycle
Indication
Regular cycles and proven ovulation.
Timing of ET
determined by detecting the spontaneous LH
surge
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Method:
1. D10-12 (3-5 d prior to estimated ovulation day) Serial US:
E thickness, follicular development and to time the
commencement of testing for LH
LH (urine) for detection of the LH surge
P levelsWhen a rise in serum LH levels is observed, it is assumed that ovulation will occur 36–40 h later (Andersen et al., 1995).
LH surges in urine lag up to 21 h behind the appearance of the surge in blood(Hoff et al., 1983; Frydman et al., 1984; Miller and Soules 1996).
The day when LH exceeds 180% of baseline (calculated as the mean of the 3 previous morning samples) corresponds to a day prior to OPU/ovulation.
2. US for evidence of ovulation.
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3. FET
3–5 days after ovulation depending on the stage
of the embryo when frozen
The day of ovulation corresponds to the day of
egg retrieval:
If embryos were frozen at 72h, ovulation day+3
is the right time to transfer. (Nawroth and Ludwig, 2005; Paulson,2011).
4. LPS:
Progesterone
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Advantage
1. Simple
2. No medications are used
3. Endocrine preparation of the endometrium is
achieved by endogenous sex steroid production
from a developing follicle
4. Preferable to many women.
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Disadvantages:
1. Even in women having regular menstrual cycles,
ovulation may not always occur
2. Problem associated with the detection of
spontaneous LH surges
A. variation in timing of its occurrence between cycles
and between patients (Park et al., 2007).
B. In order to assess the LH levels correctly,
determination should be performed at least daily, and
preferably twice a day.
C. LH urine kits have a large variation in thresholds,
which involve the risk of up to 30% of false-negative
testing, and are often reported by patients as being
difficult to interpret (Miller and Soules, 1996; Guermandi et al., 2001; O’Connor et al.,
2006).Aboubakr Elnashar
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