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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