Prediction and prevention of OHSS - an evidence-based approach Hassan N. Sallam, MD, FRCOG, PhD...

Prediction and prevention of OHSS -

an evidence-based approachHassan N. Sallam,

MD, FRCOG, PhD (London)Professor in Obstetrics and Gynaecology

The University of Alexandria, andClinical and Scientific Director,

Alexandria Fertility Center, Alexandria, Egypt

3rd Congress of Society of Reproductive Medicine, 5 – 9 October

2011, Antalya / Turkey

The old Alexandria medical school

The uterus (after Soranos of Ephesus)

Ovarian hyperstimulation syndrome (OHSS)

Rabau et al, Am J Obstet Gynecol 98: 92, 1967

Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic

complication of ovarian stimulation occurring during the luteal phase or

during early pregnancy. It is potentially fatal and is difficult to predict. Fortunately, the reported prevalence of the severe form of

OHSS is small, ranging from 0.5 to 5%.

OHSS – a potentially fatal complication

Figueroa-Casas. Extraordinary ovarian reaction to gonadotropins: fatal case. Ann Circ (Rosario): 23: 116,

1958

Schenker and Weinstein. Ovarian hyperstimulation syndrome: a current survey. Fertil Steril 30: 255, 1978

Fineschi et al. An immunohistochemical study in a fatality due to ovarian hyperstimulation syndrome. Int

J Legal Med 120: 293, 2006

Madill et al. Ovarian hyperstimulation syndrome: a potentially fatal complication of early pregnancy. J

Emerg Med 35: 283, 2008

Early and late OHSS

Early onset OHSS3 to 7 days after HCG

Excessive response to stimulation

Late onset OHSS12 to 17 days after HCG

Due to pregnancy

Lyons et al, Hum Reprod. 9: 792, 1994; Mathur et al, Fertil Steril 73: 901, 2000

Classification (grading) of OHSS

• Rabau et al, 1967• Schenker and Weinstein, 1978

• Golan et al, 1989• Navot et al, 1992

• Rizk and Aboulghar, 1999

Rabau et al, Am J Obstet Gynecol 98: 92, 1967; Schenker and Weinstein, Fertil Steril 30: 155, 1978; Golan et al, Obstet Gynecol Surv 44: 430, 1989; Navot et al, Fertil Steril 58: 249, 1992; Rizk and Aboulghar,

Textbook of IVF and ART 9: 131, 1999

OHSS grading (Golan et al, 1989)

Ovary Symptoms/ signs

Grade 1 Abdominal distension

Grade 2 5-10 cm Nausea/ vomiting

Grade 3 >10 cm Ascites

Grade 4 > 12 cm Pleural effusion

Grade 5 Haemoconcentration oliguria

Mild

Moderate

Severe

Pathophysiology of OHSSPathophysiology of OHSSPathophysiology of OHSS

Prevention of OHSS

1. Prediction of OHSS2. Primary prevention (before

starting HMG/FSH)3. Secondary prevention (after

starting HMG/FSH and before HCG administration)

Evidence-based medicine

Level A – The recommendation based on good and

consistent scientific evidence (RCT)

Level B – The recommendation is based on limited or inconsistent scientific evidence (CT, cohort,

case control)

Level C – The recommendation is based primarily on consensus and expert opinion

Prevention of OHSS




Prediction of OHSS

(A) Risk factors: PCOS, young patients, low BMI, previous OHSS, pregnancy,

genetic predisposition(B) Biochemical indices: Plasma oestradiol peak, insulin resistance, serum VEGF, von Willebrand factor,

FSH, AMH(C) Ultrasound indices: PCO pattern, high

AFC, ovarian volume, low intra-ovarian vascular resistance

Polycystic ovary syndrome(Chereau, 1844; Stein and Leventhal, 1934)

Read at a meeting of the Central Association of Obstetricians and Gynecologists, November 1 to 3, 1934, New Orleans, La

Relationship between PCOS and OHSS

Study Patients with OHSS

Controls P value

Smitz et al, 1990

50% (5/10) None (0/1663) <0.0001

MacDougall et al, 1992

63 % (5/8) None (0/1287) <0.0001

Delvigne et al, 1993

37 % (47/128) 15 % (38/256) <0.0001

Smitz et al, Hum Reprod 5: 933, 1990; MacDougall et al, Hum Reprod 7: 597, 1992; Delvigne et al, Hum Reprod 8:

1361, 1993

Relationship between age and OHSS

Study Patients with OHSS

(Age in years)

Controls(Age in years)

P value

Navot et al, 1988

27.8 ± 3.6 31.5 ± 5.7 <0.05

Lyons et al, 1994

29.7 ± 1.8 33.9 ± 0.15 <0.05


30.2 ± 3.5 32.0 ± 4.5 <0.05

Enskog et al, 1999

30.2 ± 0.7 32.5 ± 0.2 <0.05

Relationship between BMI and OHSS

Study Number of patients with

OHSS

Number of control

subjects

P value

Papanikolau et al, 2006

23.13 ± 0.8 23.05 ± 0.1 NS


22.0 ± 3.4 21.9 ± 3.2 NS

Enskog et al, 1999

23.2 ± 0.92 23.0 ± 0.16 NS

Papnikolau et al, Fertil Steril 85: 112, 2006; Delvigne et al, Hum Reprod 9: 1361, 1993; Enskog et al, Fertil Steril 71: 808,

1999

Genetic predisposition to predict OHSS

FSH receptor

FSH

FSH

http://upload.wikimedia.org/wikipedia/commons/c/cb/Follitropine.gif

Genetic predisposition to predict OHSS

Allelic frequencies

Genotypic frequencies

A T AA AT TT

Caucasian

controls

40% (78)

60 % (118)

17 % (17)

45 % (44)

38 % (37)

IVF controls

48 % (121)

52 % (131)

25 % (31)

47 % (59)

28 % (36)

OHSS patients

55 % (41)

45 % (33)

30 % (11)

51 % (19)

19 % (7)

P value NS NS NS NS NS

Daelemans et al, J Clin Endocrinol Metab 89:6310, 2004

Prediction of OHSS





Plasma E2 concentration to predict OHSS

Cut-off valueFor E2 = 2560 ng/L

For follicles >12

Papanikolau et al, Fertil Steril 85: 112, 2006

Insulin resistance to predict OHSS in PCOS

Normo-insulinaemic

(n = 21)

Hyper-insulinaemic

(n = 31)

P value

Mean total dose of HMG ± SD

(IU)

1395 ± 472 1507 ± 727 NS

Mean dose/BMI ± SD (IU/BMI)

57.7 ± 18.7 54 ± 18 NS

Ovulation rate(n/cycle)

85.7 % (18/21) 83.8% (26/31) NS

OHSS rate(n/cycle)

23.8 % (5/21) 64.5 % (20/31) <0.05 *

Pregnancy rate(n/cycle)

28.5 % (6/21) 16% (5/31) NS

Abortions(n/pregnancies)

16.6 % (1/6) 20% (1/5) NS

Felghesu et al. JCEM 82: 644, 1997

Serum VEGF to predict OHSS

Early onset OHSS

Ludwig et al, Hum Reprod 13: 30, 1998

Late onset OHSS

Von Willebrand factor to predict OHSS

Todorow et al, Hum Reprod 8: 2039, 1993

Day 3 FSH to predict OHSS

Onagawa et al, Gynecol Endocrinol 18:335-40, 2004

Pregnant Non-pregnant P value

4.4+/-1.3 mIU/ml

6.1+/-2.9 mIU/ml

0.001

OHSS No OHSS P value

4.5+/-1.2 mIU/ml

5.9+/-2.8 mIU/ml

0.003

Cut-off point = 5.25 mIU/ml

AMH to predict OHSS

Lee et al. Hum Reprod 23: 160, 2008

AMH Age

BMI

Cut-off value 3.36

ng/ml

Cut-off value 33

years

Cut-off value 18.44

Kg/m2

AMH to predict ovarian response

Early follicular Mid-luteal

Cut-off (ng/mL) 2.7 2.7

Sensitivity (%) 83.3 91.7

Specificity (%) 82.4 88.2

PPV (%) 76.9 84.6

NPV (%) 87.2 93.8

Accuracy (%) 82.8 89.6

Elgindy et al, Fertil Steril 89:1670, 2008

Prediction of OHSS





PCO pattern to predict OHSS

Rizk and Smitz, Hum Reprod 7: 320, 1992; Delvigne et al, Hum Reprod 8: 1353,

1993

Antral follicle count(Tomas et al, 1997)

• Transvaginal ultrasound• After ovarian suppression with GnRHa and before starting FSH

• Follicles 2 to 5 mm in both ovaries• Patients with <5 follicles in both

ovaries were poor responders

Tomas et al, Hum Reprod 12(2):220, 1997

Trans-vaginal scan showing antral follicles

Right ovary Left ovary

AFC to predict ovarian response

Kwee et al, RBEJ 5:9, 2007

Total AFC

Sensitivity

Specificity

PPV Accuracy

<4 0.21 0.99 0.86 0.78

<5 0.28 0.99 089 0.80

<6 0.41 0.95 0.75 0.89

<7 0.69 0.80 0.56 0.77

<8 0.76 0.74 0.51 0.75

AFC to predict poor responders


Total AFC

Sensitivity

Specificity

PPV Accuracy

<10 0.94 0.71 0.36 0.76

<12 0.88 0.80 0.44 0.81

<14 0.82 0.89 0.58 0.88

<16 0.47 0.96 0.67 0.88

<18 0.29 0.98 0.71 0.87

AFC to predict hyper responders


AFC versus AMH to predict poor response

Hendricks et al, Fertil Steril 83(2): 291, 2005Broer et al, Fertil Steril 91: 705, 2009

AMH

AFC

AFC v/s AMH to predict hyper-response

Broer et al, Hum Reprod Update 17: 46, 2011

AFC

AMH

Predictors of OHSS (Sallam et al, 2011)

OHSS No OHSS P value

No. of cycles 11 22

Day 3 FSH (mIU/ml) 5.97 (2.05) 9.31 (3.01) 0.204

Day 3 LH (mIU/ml) 6.70 (3.14) 5.74 (3.64) 0.230

Day 3 E2 (pg/ml) 38.67 (14.41) 34.66 (9.00) 0.33

Day 3 leptin (ng/ml) 40.27 (28.06) 44.77 (25.71) 0.324

Day 3 VEGF (pg/ml) 438.00 (178.08)

448.27 (216.81)

0.446

Day 3 AFC 21.64 (3.20) 14.32 (3.81) < 0.0002*

Day 3 AMH (ng/ml) 4.50 (2.87) 2.17 (1.55) < 0.005*

E2 on HCG day (pg/ml)

5965.82 (1191.99)

2207.27 (659.32)

< 0.0001*

Sallam et al, Predictors of OHSS, submitted for publication

ROC curves comparing AMH and AFC

Sallam et al, Predictors of OHSS, submitted for publication

AFC

AMH

Cut-off value =>14

Cut-off value 3.36

ng/ml

Ovarian volume

Age Group

Mean Ovarian volume

(ml)

SD (ml)95%

Confidence Interval

% Ovaries Imaged

1 day to 3 months

1.06 0.96 0.03-3.56 70

4-12 months 1.05 0.67 0.18-2.71 100

13-24 months

0.67 0.35 0.15-1.68 90

2 -12 years 0.46 - 0.13-0.9 (range) -

13-20 years 4.0 - 1.8-5.7 (range) -

Cohen et al, AJR 160: 583, 1993; Orsini et al, Radiology 153:113, 1984; Sample et al. Radiology 125:477, 1977; Ivarsson et al, Arch

Dis Child 58, 352, 1983

Ovarian volume

Ivarsson et al, Arch Dis Child 58, 352, 1983

3-D U/S in obstetrics and gynaecology

Ovarian volume to predict OHSS

OHSS Controls P value

No. of patients 8 86

Days of stimulation 10.5 ± 2.5 10.5 ± 1 8 NS

Oestradiol (pg/ml) 2439 ± 1350 937 ± 686 0.0001

No. of follicles 23.3 ± 4.3 13.8 ± 7.5 0.0025

No. of oocytes 164 ± 26 5.9 ± 3 0 0.0001

Cycle length 34.1 ± 5.8 28.7 ± 2 2 0.0001

Body wt before stimulation

55.4 ± 3.8 62.8 ± 11 0.011

Body wt after stimulation 54 3 ± 4.5 62.9 ± 10. 7 0.03

Ovarian volume (ml) 13.2 ± 5 8.9 ± 3.7 0.035

Danninger et al, Hum Reprod 11: 1597, 1996

Perifollicular blood flow to predict OHSS

Oyesanya, Fertil Steril 65: 874, 1996

Intrafollicular hemodynamics to predict OHSS

OHSS Controls P value

Mean age (years) 32.63 ± 1.77 31.48 ± 3.87 NS

Mean duration of infertility (years)

6.00 ± 2.19 5.29 ± 2.73 NS

Maximal peak systolic velocity

0.15 ± 0.04 0.21 ± 0.10 NS

Mean minimal pulsatility index

0.89 ± 0.30 0.79 ± 0.14 NS

Mean minimal resistance indexes

0.56 ± 0.05 0.53 ± 0.06 NS

Oyesanya, Fertil Steril 65: 874, 1996

Combination of indices to predict OHSS

Regression analysis showed that the dependent factors were: (1) Log oestradiol, (2) Slope of log oestradiol, (3) HMG dosage, (4) No. of oocytes

retrieved and (5) LH/FSH ratio. The following formula was devised:

Delvigne et al, Hum Reprod 8: 1353, 1993

PPV = 78.5 %; FNR = 18.1%

Conclusion 1 - PredictionGood

predictorsBad predictors Further

evaluation

PCOS Genetic predisposition

PCO pattern

Young age Serum VEGF BMI

AFC Von Willebrand factor

Day 3 FSH

E2 level on day of HCG

Perifollicular blood flow

Insulin resistance

Ovarian volume

AMH

Prevention of OHSS




Primary prevention (before starting HMG/FSH)

• FSH or HMG• Low dose step-up protocol

• Step-down protocol• Alternate day HMG/FSH

• Sequential protocol• In-vitro maturation (IVM)

• GnRH antagonists

Nugent et al, Cochrane Database: Issue 1, 2009

FSH versus HMG to prevent OHSS

Chronic low-dose step-up protocol

Homburg et al, Fertil Steril 63: 729, 1995

Low dose step-up protocol (RCT)

Conventional Step-up P value

No. of cycles 48 49

Oestradiol on the day of HCG (pg/ml)

1258.6 ± 1003 533.5 ± 525

0.001

No. of pregnancies 7 (14.6%) 7 (14.3%) NS

No. of abortions 1 (14.3%) 1 (14.3%) NS

No. of multiple pregnancies

2 (28.6%) 1(14.3%) NS

No. of OHSS 13 (27.1%) 4 (8.3%) 0.05

Mild OHSS 5 (10.4%) 4 (8.3%) NS

Moderate OHSS 8 (16.7%) 0 (0%) 0.01

Sengoku et al, Hum Reprod 14: 349, 1999

Step-down protocol

Mizunuma et al, Fertil Steril 55: 1195, 1991

Step-up, step-down and conventional protocols (RCT)

Protocol Conventional (n =

19)

Step down (n = 24)

Step up

(n = 25)

P value

Small follicles 7.6 ± 1.9 * 6.3 ± 1.0 3.1 ± 0.7 *

<0.05

Medium follicles

5.7 ± 1.2 * 5.0 ± 0.8 2.3 ± 0.6 *

<0.05

Large follicles 1.5 ± 0.3 1.2 ± 0.2 1.3 ± 0.3 NS

Andoh et al, Fertil Steril 70: 840, 1998

Santbrink and Fauser, J Clin Endocrinol Metab 82: 3597, 1997

Step-up versus step-down protocol (RCT)

Step-up (n=18) Step down (n=17)p

Step-up versus step-down protocol (RCT)

Low dose step-up

Step down P value


Duration of treatment

(days)

18 9 0.003

No. of ampoules 20 14 NS

Monofollicle growth

6 (39%) 17 (100 %) < 0.001

Ovulation rate 84 % 89 % NS

Ongoing pregnancies

2 5 NS

OHSS 0 0 NS

Santbrink and Fauser, J Clin Endocrinol Metab 82: 3597, 1997

Chronic low-dose step-up versus step-down protocol (RCT)

Low dose step-up

Step down P value


Duration of treatment

(days)

15.2 ± 7 9.7 ± 3.1 < 0.001

Total dose of rec-FSH (IU)

951 ± 586 967 ± 458 NS

Mono-follicular growth

68.2% 32% < 0.0001

Ovulation rate 70.3% 61.7% 0.02

Pregnancies/cycle

18.7% 15.8% NS

OHSS 2.25% 11% <0.001

Christian-Maitre et al, Hum Reprod 18:1626, 2003

Alternate day HMG to prevent OHSS

Nugent et al, Cochrane Database: Issue 1, 2009

Sequential FSH regimen to prevent OHSS (RCT)

Step-up protocol

step-down

protocol

Sequential protocol

P value

No. of cycles 75 75 75

No. of clinicalpregnancies (rate)

18 20 33 <0.05

Pregnancy rate 31.0 % 32.2 % 48.5 % NS

No. of multiplepregnancies (rate)

4 (22.2%) 5 (25.0%) 8 (24.0%) NS

NS

Rate of hyperstimulation

5.2 % 13 % * 5.9 % <0.05

Koundouros, Fertil Steril 90: 569, 2009

In-vitro maturation to prevent OHSS (CCT)IVM IVF OR (95% CI)

No. of cycles 107 107

Implantation rate (%) 9.5 17.1 0.51 (0.31, 0.84) *

Clinical pregnancy [n (%)]

23 (21.5) 36 (33.7) 0.54 (0.28, 1.04)

Live birth [n (%)] 17 (15.9) 28 (26.2) 0.53 (0.26, 1.10)

Multiple live births [n (% of total live births)]

7 (41.2) 10 (37.0) 1.26 (0.30, 5.11)

Moderate or severe OHSS

0 12 (11.2%)

0.036 (0.002-0.608) *

Child et al, Obstet Gynecol 100: 665, 2002

GnRHa v/s antagonists to prevent OHSS, 2009

Al-Inany et al, Cochrane Database: Issue 1, 2009

LBR in GnRH agonists v/s antagonists, 2009

Al-Inany et al, Cochrane Database: Issue 1, 2009

GnR a v/s antagonists to prevent OHSS, 2011

Al-Inany et al, Cochrane Database Syst Rev 11;(5):CD001750, 2011

LBR in GnRH agonists v/s antagonists, 2011

Al-Inany et al, Cochrane Database Syst Rev 11;(5):CD001750, 2011

Conclusion 2 – Primary prevention

The following approaches are associated with a lower incidence of OHSS:

• FSH compared to HMG (without GnRHa) (A)• Step-up compared to conventional protocol

(A)• GnRH antagonists compared to agonists (A)• IVM compared to IVF but with a lower LBR

(B)• Sequential compared to step down protocol

(A)

Conclusion 2 – Primary prevention

(cont…)The following approaches are equivocal in

the primary prevention of OHSS:• Alternate days compared to conventional

protocol (A) • Sequential compared to step-up protocol

(A)

The following approaches need further evaluation:

• Step-up compared to step down protocol

Prevention of OHSS




Late prevention (after starting HMG/FSH and before HCG)

• Cancellation of the cycle• Coasting

• Diminish HCG dose• GnRHa to trigger ovulation

• Metformin• Albumin

• Cabergoline• I.V. Calcium

• Cryopreservation of embryos• GnRH agonists + embryo freezing• Unilateral follicle aspiration before

HCG• Laparoscopic ovarian electro-

cautery

Cancellation of the cycle - attitude of 141 physicians

High risk patient

Moderate risk

patient

Low risk patient

P value

Proceed with IVF 8 % 22 % 38 % <0.001

Cancel cycle 14 % 14 % 7 % NS

Take some preventive measures

78 % 64 % 55 % <0.01

Delvigne and Rozenberg, Hum Reprod 16: 2491, 2001








cautery

Coasting to prevent OHSS - Guidelines

1. Start at • Serum E2 >4,500 pg/mL

• E2 production >150 pg/follicle 16–18 mm • >15 mature follicles

2. Measure E2 on a daily basis3. Give hCG when E2 level falls to <3,500

pg/mL 4. Abandon if

• E2 level rises to >6,500 pg/mL• >30 mature follicles

• Coasting takes >4 daysGarcia-Velasco et al, Fertil Steril 85:

547, 2006

Incidence of OHSSOR = 0.53 (95% CI = 0.23 to 1.23)

Live birth rateOR = 0.48 (95% CI = 0.14 to 1.62)

Clinical pregnancy rate

OR = 0.69 (95% CI = 0.44 to 1.08)

Oocytes retrieved OR = -3.92 (95% CI -4.47 to -3.37) *

Coasting to prevent OHSS (Cochrane)

D’Angelo et al, Cochrane Database Syst Rev 15;(6):CD002811, 2011








cautery

Diminish HCG dose (OS)

• 21 infertile patients at risk of OHSS • Low dose of HCG (i.e. 2500 IU)• No moderate or severe OHSS• 13 women (61.9%) conceived

• Three twin pregnancies

Nargund et al. RBMOnline 14: 682, 2007








cautery

Incidence of OHSS after GnRH agonists to trigger ovulation (MA)

Reference

No patients

with agonist trigger

No of patients with hCG trigger

Patients with OHSS post

agonist

Patients with OHSS

post hCG (%)

P value

Babayof et al, 2006

(RCT)15 13 0/15 4/13 (31%) <0.05

Engmann et al, 2008

(RCT)33 32 0/33

10/32 (31%)

<0.001

Acevedo et al, 2006

(RCT)30 30 0/30 5/30 (17%) <0.05

TOTAL 78 75 0/7819/75 (25%)

<0.001

Kol and Solt, JARG 25: 63, 2008

GnRH agonists to trigger ovulation

Griesinger et al, Human Reprod Update 12: 159, 2006

GnRH agonists to trigger ovulation

Youssef et al, Cochrane Database Syst Rev 10;(11):CD008046, 2010

OHSS incidence per randomised woman OR =

0.10 (95% CI = 0.01 to 0.82) *

GnRH agonist versus HCG (LBR)

OR = 0.44 (95% CI = 0.29 to 0.68) *

GnRH agonist versus HCG (OPR) OR = 0.45 (95% CI = 0.31 to 0.65) *

GnRH agonists to trigger ovulation with modified luteal support (OS)

No OHSS after GnRHa triggering 5% risk

difference (with 95% CI: -0.07 to 0.02)

Delivery rate after modified luteal support 6% risk difference (95% CI: -0.14 to 0.2)

Delivery rate after conventional luteal support 18% risk difference (95% CI: -0.36 to 0.01)

Humaidan, Hum Reprod Update 17(4):510-24, 2011








cautery

Costello et al. Hum Reprod 21:1387, 2006

Metformin versus placebo or no treatment in IVF for to prevent OHSS in PCOS

patients

OR = 0.21; 95% CI = 0.11–0.41, P < 0.00001








cautery

Albumin for the prevention of OHSS

Aboulghar et al, Cochrane Database: Issue 1, 2009

Hydroxyethyl starch (HES) to prevent OHSS (CCT)

HES Control group P value


No. of pregnancies

28 24 NS

Moderate OHSS 10 32 <0.00001

Severe OHSS 2 7 NS

Graf et al, Hum Reprod 12: 2599, 1997

HES versus albumin to prevent OHSS (RCT)

HES (n = 85)

Albumin (n =82)

Control group (n =

83)

P value

Moderate OHSS

5 (5.9 %) 4 (4.9 %) 12 (14.5 %) <0.05

Severe OHSS

0 0 4 (4.8 %) <0.05

Overall cases of

OHSS

5 (5.9 %) 4 (4.89 %) 16 (19.2 %) <0.01

Gokmen et al, Eur J Obstet Gyn Reprod Biol 96: 187, 2001








cautery

Effect of cabergoline on rats with OHSS

A = Vascular permeabilityB = Serum prolactinC = Plasma progesteroneGomez et al, Endocrinol 147:

5400, 2006

Cabergoline inactivates the VEGF receptor 2 (VEGFR-2)

Cabergoline to prevent OHSS (RCT)

Albumin + Cabergoline

Albumin only

P value


Early OHSS 0 12 (15.0 %) < 0.001

Late OHSS 9 (10/8 %) 93(3.8 %) NS

Carizza et al, RBMOnline 17: 751, 2008








cautery

I.V. Calcium to prevent OHSS (CCT)

I.V. Calcium Control group

P value


OHSS 3 (3.6%) 60 (16.2%) <0.01

Pregnancies (CPR)

34 (40.5%) 107 (28.8%) <0.05

Deliveries (LBR) 32 (38.1%) 92 (24.8%) <0.02

Gurgan et al, Fertil Steril 96: 53-7, 2011








cautery

Embryo freezing to prevent OHSS

D’Angelo and Amso, Cochrane Database: Issue 2, 2002








cautery

GnRH agonists + embryo freezing to prevent OHSS (OS)

% (n) 95% CI

Biochemical PR/patient 5.3 % (1/19) 0.9 % – 24.6 %

Ongoing PR/patient 36.8 % (7/19) 19.1 % – 59.0 %

Ongoing PR/first ET 31.6 % (6/19) 15.4 % – 54.0 %

Cumulative ongoing PR/ET

29.2 % (7/24) 14.9 % – 49.2 %

OHSS 0 % (0/24)

Griesinger et al, Human Reprod 22: 1348, 2007








cautery

Unilateral follicle aspiration before HCG (RCT)

Unilateral follicle

aspiration (n = 16)

Controls (n = 15)

P value

Oestradiol (pmol/l)

15 982 ± 827 16 243 ± 593 NS

Mild OHSS 1 3 NS

Moderate OHSS 1 1 NS

Severe OHSS 2 1 NS


6/16 (37.5%) 7/15 (46.6%) NS

Egbase et al, Hum Reprod 12: 2603, 1997








cautery

Laparoscopic ovarian electro-cautery (RCT)Conventional

IVF(n = 25)

LOE + IVF(n = 25)

P value

Cancellations due to OHSS risk

5 0 0.025 *

Moderate OHSS 4 1 0.174

Mean number of oocytes 7.37 10.28

Mean embryos transferred 2.5 2.6

Pregnancy rate/cycle 8/25 (32.0 %) 9/25 (36.0 %)

0.765

Rimington et al, Hum Reprod 12: 1443, 1997

Conclusion 3 – Secondary prevention

The following approaches prevent OHSS:• Triggering ovulation with GnRH agonists (A)

• Metformin administration (A)• Intravenous albumin (A)• Hydroxyethyl starch (A)

• Cabergoline for early OHSS (A)• Laparoscopic ovarian electrocautery (A)

The following approaches do not prevent OHSS

• Coasting (A)• Cabergoline for late OHSS (A)

Conclusion 3 – Secondary prevention (cont…)

The following approaches are equivocal in preventing OHSS:

• Coasting versus unilateral oocyte aspiration (A)

• GnRH antagonists versus coasting (A)

The following approaches await further evaluation:

• Cancellation of the cycle•Diminishing the dose of HCG

• Embryo freezing• Triggering with GnRHa + embryo freezing

Prediction and prevention of OHSS -

an evidence-based approachHassan N. Sallam,

MD, FRCOG, PhD (London)Professor in Obstetrics and Gynaecology

The University of Alexandria, andClinical and Scientific Director,

Alexandria Fertility Center, Alexandria, Egypt

3rd Congress of Society of Reproductive Medicine, 5 – 9 October

2011, Antalya / Turkey

Coasting to prevent OHSS (OS)


Coasting to prevent OHSS (OS)

Characteristic Outcome

No. of patients 15

Mean age (years ) ± SD 33.5 ± 2.8

Body mass index ± SD 34.8 ± 5.2

No. of ampoules ± SD 50.2 ± 16.5

Moderate OHSS (%) 3 (20 %)

Severe OHSS 3 (20 %)

Clinical pregnancy rate 5/15 (33.3 %)


Coasting versus early unilateral follicular aspiration to prevent

OHSS

D’Angelo and Amso, Cochrane Database Issue 1, 2009

GnRH antagonists versus coasting to prevent OHSS (RCT)

Coasting(n = 96)

GnRH antagonist

(n = 94)

P value

No. of high quality embryos (SD)

2.21 ± 1.1 2.87 ± 1.2 <0.0001

Mean number of oocytes (SD)

14.06 ± 5.20 16.5 ± 7.60 <0.02


47.9 % 55.3 % NS

Severe OHSS None None NS

Aboulghar et al, RBMOnline 15: 271, 2007

Conclusion 1 - Prediction

Good predictors Bad predictors

PCOS BMI

Young age Genetic predisposition

PCO pattern Serum VEGF

AFC Von Willebrand factor

E2 level on day of HCG Perifollicular blood flow

Insulin resistance

Large ovarian volume

AMH

Prediction and prevention of OHSS - an evidence-based approach Hassan N. Sallam, MD, FRCOG, PhD...

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Transcript of Prediction and prevention of OHSS - an evidence-based approach Hassan N. Sallam, MD, FRCOG, PhD...