Dr. Hakan ÖZÖRNEKEUROFERTIL

Reproductive Health Center

OHSSOHSS is an iatrogenic complication of

ovulation induction.The syndrom can result in serious life

treatening complications The syndrom charecterized by leakage of

fluid from the intravascular compartment, with accumulation in the peritoneal and pleural cavities, resulting in hypotension and a decrease in renal blood flow and volume of urine.

ClassificationMild OHSS

Grade 1 Abdominal distention and discomfortGrade 2 + nausea, vomiting and/or diarrhoea

Moderate OHSSGrade 3 + ultrasonic evidence of ascites

Severe OHSSGrade 4 + clinical evidence of ascites and/or

hydrothorax or dyspnoeaGrade 5 + haemoconcentration, coagulation

abnormalities, diminished renal perfusion

Prevention

1. Step Identification of risk factors

2. Step Monitoring the ovarian response (US+E2)

Risk factors for OHSSPCOSHigh number of antral follicles at day3

(>10/ovary)Enlarged ovarian volumeLH/FSH > 2HyperandrogenismYoung age < 35Low body weightPrevious ocurrence of OHSS

Prevention by PCOSDiet – weight loseMetforminOvarian drillingNonstimulated – natural cycleIVMOral ovulation inductionLow dose gonadotropin

MetforminNo metformin

(n=159)Metformin

(n=128)

Age 34.8 33

BMI 27.2 27.8

HMG ampoules 37.1 41.1

Oocytes retrieved 23.8 18.8

Embryos tranferred 2.8 3

Clinical pregnancies 37.6 30.5

Moderate and severe OHSS*

20 1

Khattab, Reprod Biomed Online, 2006

Prevention of OHSSWithholding hCG ‘cancelling’Delaying hCG ‘coasting’Modification of methods to trigger ovulationEarly unilateral follicular aspirationProgesterone for luteal phase supportCryopreservation of all embryosGradual and slow hMG protocol in PCOSAlbumin administration at time of retrievalGlucocorticoid administration

Canceling CycleshCG triggers the development of OHSSWithholding hCG is the only method that

totally avoids the risk of OHSSSerum E2 level upper limit 4000 pg/mlAfter stopping the gonadotrophin treatment

the GnRH agonist or antagonist should be continiued until the ovaries recover to normal size

Modification of methods to trigger ovulationDecrease in hCG dose

10.000 IU vs. 5.000 IU or 3.000 IU no differenceGnRHa

Used in antagonist cycle, as effective as hCG, decreased insidence of OHSS but significant less pregnancy

rLHPRT multicenter hCG vs rLH significantly fewer

moderate and severe cases of OHSSrhCG

Folicular aspirationFolicular aspiration at the time of oocyte

retrieval had no protective effect of OHSSUnilateral folikular aspiration prior to HCG

also does not reduce the incidence of severe OHSS

Glucocorticoid administration

Because of conflicting reports in the literature there are currently insufficient data to recommend glucocorticoid administration

Methylprednisolon (n=50)

Untreated (n=41)

Age 30.5 30.9

E2 concentration* pg/ml

4848 3727

Oocytes retrieved* 28.7 24

Embryos transferred 3.9 4.0

OHSS* 10% 43.9%Lainas et al., Fertil Steril, 2002

Lutheal phase supportLutheal phase support with hCG increases

the incidence of OHSS. Progesterone intravaginally or im should be

used for the patients at risk of OHSS

CoastingFirst described and applied by Sher et al in

1993hCG administration postponed until the

patients serum E2 level decreases to a safer zone.

Significantly higher percentage of granulosa lutein cells become apoptotic after coasting. E2 levels usually to rise rapidly in the 48 h following initiation of the coasting period, then plateaued and began to fall 96-168 h after the gonadotropins were stopped.

CoastingCochrane review identified 13 studies of

which only one trial met the inclusion criteria.

There was no difference in the incidence of moderate and severe OHSS and in the clinical pregnancy rate between the groups.

D’Angelo et al., Cochrane Library, 2002

Coasting durationCoasting < 4 days

(n=983)Coasting >4 days

(n=240)

Age 30.2 29.9

Oocytes retrieved* 16.5 14.9

Mean no of embryos trans

2.99 3.03

Clin pregnancy rate* 52.0 35.9

Implantation rate* 26.3 18.2

Mansour, et al., Fertil Steril, 2005

Coasting (Practical guidelines)Start at

Serum E2>4500 pg/ml> 15 and < 30 mature follicles

Measure E2 on a daily basis, do not skip any day to avoid sudden unexpected drops

Give hCG when E2 level falls to < 3500 pg/mlAbandone if

E2 level rises to >6500 pg/ml> 30 mature folliclesCoasting takes > 4 days

CoastingCoasting is a good alternative that can avoid

cycle cancellation in high responders, who have high risk of developing severe OHSS

Even if OHSS develops after coasting both its incidence and severity will be diminished

Cryopreservation of all embryosInsted of canceling the cycle after the

administration of hCG retrieve the oocytes and than cryopreserve all embryos

Cochrane review identified 17 studies, two of which met the inclusion criteria.

When elective cryopreservation was compared with fresh embryo transfer no difference was found between the two groups in the incidence of OHSS.

There is insufficient evidence to support routine cryopreservation.D’Angelo et al., Cochrane Library, 2002

Albumin administrationAlbumin is prevent the development of OHSS

by increasing plasma oncotic pressure and binding of OHSS mediators of ovarian origin

The cochrane review shows a clear benefit from administration of iv albumin at te time of oocyte retrieval in prevention of severe OHSS in high risk cases.

For every 18 women at risk of severe OHSS albumin infusion will save one more case

Albumin is a human product!

D’Angelo et al., Cochrane Library, 2002

HES (Hydroxyethyl starch solution) administrationSynthetic macromolecules used to prevent

OHSS and avoid the potential risks from using human products such as albumin

HES is effective volume expander. It is as effective as albumin

It is cheaper and safer

ConclusionOHSS is a serious complication of ovarian

stimulationThe identification of high risk patients and in

particular PCOS patients and the use of low dose protocols of ovarian stimulation have an important role in the prevention of OHSS

To date no methods are available to completly prevent this complication except for withholding hCG.

ConclusionCoasting for at least as long as 3 days can be

successfully used in the prevention of OHSSIt appears that iv albumin administered at

the time of oocyte retrieval may help the prevention of OHSS

The effect of combining methods which act at two different levels (eq. coasting and HES administration) helps for a better prevention

There is a clear need for large randomised studies