Predisponerende factoren van OHSS

Publicatiedatum: 02-01-2026

Beoordeeld op geldigheid: 02-01-2026

Uitgangsvraag

Wat zijn de predisponerende factoren van OHSS?

Aanbeveling

Wees alert op een mogelijk verhoogd risico op OHSS bij vrouwen met een jonge leeftijd, lage BMI, hoge antrale follikeltelling, hoge serum AMH waarde en een hoge follikeltelling of serum oestradiol tijdens stimulatie.

Overwegingen

Voor- en nadelen van de interventie en de kwaliteit van het bewijs

In de literatuuranalyse werd onderzocht wat predisponerende factoren zijn van OHSS. Er werden geen studies gevonden die afkapwaarden van predisponerende factoren hebben onderzocht in combinatie met een effect op gezondheidswinst door preventie of verandering van therapie bij vrouwen die een IVF, (PGT-)ICSI of een eicelvitrificatie behandeling ondergaan. Ook werden er geen studies gevonden met voorspellende modellen waarbij er interne of externe validatie van de modellen plaatsvond. Wel werden 20 observationele studies gevonden die predisponerende factoren beschreven.

Uit de 20 observationele studies werden de volgende factoren geassocieerd met risico op OHSS.

Geassocieerde factoren die bekend zijn voorafgaand aan de IVF/(PGT-)ICSI/eicelvitrificatie behandeling:

Jonge leeftijd
Hoog serum AMH
Hoge antrale follikeltelling
Lage BMI
Diagnose PCOS

Geassocieerde factoren die bekend worden gedurende de IVF/(PGT-)ICSI/eicelvitrificatie behandeling:

Hoog aantal groeiende en geaspireerde follikels
Hoog serum oestradiol

Zoals beschreven zijn de resultaten van de geïncludeerde studies heterogeen (Table 1) en niet gevalideerd en is er geen meta-analyse van de data mogelijk. Het is daarom niet mogelijk om een eenduidige afkapwaarde vast te stellen van de predisponerende factoren met een bijbehorend risico op OHSS.

Uit de OPTIMIST trial (Oudshoorn et al, Human Reproduction, 2017) is gebleken dat het verlagen van de standaard dosering van FSH (naar 100 IE in plaats van 150 IE) bij vrouwen met een antrale follikeltelling >15 leidt tot een vergelijkbaar cumulatief zwangerschapspercentage en een verminderd aantal gevallen van OHSS. De studie vond geen verschil in incidentie van ernstige OHSS tussen de twee behandelgroepen.

In een Cochrane analyse (Youssef et al., Cochrane Database Syst Rev 2014) met een meta-analyse van 8 RCT’s is aangetoond dat het gebruik van een agonist trigger in vergelijking tot een hCG trigger leidt tot een vermindering van het aantal gevallen van OHSS in vrouwen die als hoog risico worden ingeschat (OR 0.15, 95% CI 0.05-0.47). Patiënten werden ingeschat als ‘hoog risico’ in het geval van een diagnose PCOS of de aanwezigheid van ≥14 follikels ≥11 mm. Gebruik van een agonist trigger wordt geassocieerd met een lagere kans op een levendgeboren kind na verse ET (OR 0.47, 95% CI 0.31-0.70); derhalve dient bij toepassing van een agonist trigger een ‘freeze-all’ beleid gehanteerd te worden.

Waarden en voorkeuren van patiënten (en evt. hun verzorgers)

Het belangrijkste doel van de interventie is het streven naar een doorgaande zwangerschap op een zo veilig mogelijke manier. Inzicht in de risicofactoren van OHSS kan voor een patiënt behulpzaam zijn, om zo gezamenlijk met de arts tot een behandeling te komen en om een verwachting te scheppen voor de uitkomst van de behandeling.

Kosten (middelenbeslag)

De beschreven risicofactoren worden relatief standaard bepaald voorafgaand aan en tijdens ovariële stimulatie en het meenemen hiervan zal daarom ook geen invloed hebben op de kosten van een behandeling. Een kosten-baten analyse van het aanpassen van de FSH dosering leidde niet tot een verschil in kosten van de behandeling voor 150 of 100 IE FSH (van Tilborg et al., Human Reproduction, 2018).

Aanvaardbaarheid, haalbaarheid en implementatie

Bij het opzetten van een ovarieel hyperstimulatie doseer schema wordt bij voorbaat al routinematig kennisgenomen van geïdentificeerde risicofactoren voor OHSS zoals leeftijd en antrale follikeltelling. Het is derhalve haalbaar en reeds gangbaar om hier rekening mee te houden in de planning van FSH dosering en beleid.

Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies

Daar de afkapwaarden van de gerapporteerde risicofactoren in de literatuur zeer divers zijn, kunnen er geen universele afkapwaarden worden gedefinieerd en dient het risico op OHSS individueel te worden afgewogen.

Onderbouwing

Achtergrond

One of the most consequential complications of ART is the development of OHSS. To gain a better understanding of which patient is at risk for OHSS, it is important to know which factors are predictive of OHSS occurrence. In this way, the treatment can be adjusted to prevent the development of OHSS and follow-up can be tailored to the patient.

Conclusies / Summary of Findings

Since there was no internal or external validation of the study, only descriptive data is provided, and no GRADE assessment is performed.

Samenvatting literatuur

Since there was no internal or external validation of the study, only descriptive data is provided, and no GRADE assessment is performed.

Zoeken en selecteren

A systematic review of the literature was performed to answer the following question:

What predisposing factors are there for the development of OHSS in women undergoing IVF or ICSI treatment?

P (Patients):	Women undergoing IVF, (PGT-)ICSI or egg vitrification treatment
I (Intervention):	Presence of possible predisposing factors: PCOS, large number of follicles (AFC) before start of treatment, number of follicles, number of eggs, age < 35, low body weight, high or rapidly increasing level of estradiol (14000) before an ovulation trigger and occurrence of pregnancy
C (Control):	Absence of predisposing factors
O (Outcome measure):	Developing OHSS, complications of OHSS, fertility outcomes, pregnancy outcomes and possible side effects of the intervention
T (Timing):	At the time of treatment schedule preparation or response to ovarian hyperstimulation (during current treatment or known response to previous treatment)
S (Setting):	A fertility center (2nd, 3rd line but also commercial fertility clinics)

Relevant outcome measures

The guideline development group considered developing OHSS as a critical outcome measure for decision making; and secondary complications of OHSS, fertility outcomes, pregnancy outcomes and possible side effects of the intervention as important outcome measures for decision making.

The working group defined the outcome measures as follows:

Developing OHSS: with or without hospital admission
Complications of OHSS: edema with or without drainage (ascites drainage/pleural drainage), hydrothorax, dyspnoea, thromboembolic event, enlarged ovary, ovarian torsion, oliguria, anuria, kidney failure, liver failure, sepsis
Fertility outcomes: ongoing pregnancy

For the other outcomes, the working group did not define the outcome measures a priori but used the definitions used in the studies.

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms from 2000 until the 10^th of October, 2023. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 1001 hits. Studies were selected based on the following criteria:

Systematic review (searched in at least two databases, and detailed search strategy, risk of bias assessment and results of individual studies available), or observational studies assessing predisposing factors for OHSS.
Full-text English language publication and
Studies according to PICO.

Fifty-two studies were initially selected based on title and abstract screening. After reading the full text, thirty-two studies were excluded (see the table with reasons for exclusion under the tab Methods), and twenty studies were included.

Results

Twenty observational studies resulting from the literature search were included in the literature analysis. Since no internal or external validation was performed in these studies, no evidence table or risk of bias table were provided, but only descriptive data were presented.

Table 1. Characteristics of included studies

Author (year)	Population	Outcome	Predisposing factors	Model characteristics
Aghssa, 2015	Long GnRH agonist Controlled Ovarian Hyperstimulation (n=105)	OHSS	The number of retrieved oocytes: OR=1.3 (95%CI 1.1 to 1.6) Basal AMH value: OR=5.4 (95%CI 1.1 to 27.9) Follicle count: OR=1.5 (95%CI 1.1 to 1.9) Corrected for: not reported	AMH-level AUC: 0.86 (95%CI 0.78 to 0.95) Cut-off value 6.95 ng/l (sensitivity=75%, specificity=84%, PLR=4.7, NLR=0.3)
Aramwit, 2008	Women (n=117) undergoing ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection with recombinant follicle-stimulating hormone either follitropin-b or follitropin-a	Moderate to severe OHSS	Serum E2 peak concentration of ≥4500 pg/mL: OR=1.15 (95%CI 1.02 to 1.29) Total number of oocytes retrieved of ≥15: OR=1.74 (95%CI 1.18 to 2.58) Corrected for: not reported	Sensitivity=75.0% Specificity: 100.0% PPV: 100.0% NPV: 97.2%.
Ashrafi, 2015	86 NPCOS* patients with moderate-to-severe OHSS and 172 NPCOS patients without OHSS who underwent in vitro fertilization and/or intracytoplasmic sperm injection	Moderate to severe OHSS	Age: OR=0.9 (95%CI 0.81 to 0.99) Antral follicles count: OR=4.3 (95%CI 2.7 to 6.9) Corrected for: not reported	Regression model based on primary demographic, medical history, and clinical characteristics: AUC: 0.94 (95%CI 0.91 to 0.97) Sensitivity: 88.1% (95%CI 79.2 to 94.1) Specificity: 87.9% (95%CI 81.6 to 92.7) Serum E₂ level on HCG day: AUC: 0.95 (95%CI 0.92 to 0.98) Cut-off value: 2045 Sensitivity: 96.5% (95%CI 90.1 to 99.3) Specificity: 83.7% (95%CI 77.0 to 89.2) Total number of follicles ³12 mm on HCG day: AUC: 0.94 (95%CI 0.90 to 0.96) Cut-off value: 17 Sensitivity: 81.4% (95%CI 71.6 to 89.0) Specificity: 98 (95%CI 94.4 to 99.6)
Griesinger, 2016	Patients undergoing ovarian stimulation on day 2 or 3 of their menstrual cycle with corifollitropin alfa treatment (n=2344)	Moderate to severe OHSS	Moderate to severe OHSS: Number of follicles ³11 mm: OR=1.113 (95%CI 1.081 to 1.147) Estradiol: OR=1.165 (95%CI 1.106 to 1.227) Both factors: OR=1.090 (95%CI 1.026 to 1.157) Severe OHSS: Number of follicles ³11 mm: OR=1.105 (95%CI 1.064 to 1.148) Estradiol: OR=1.190 (95%CI 1.115 to 1.270) Both factors: OR=1.129 (95%CI 1.049 to 1.216) Corrected for: not reported	Moderate to severe OHSS Number of follicles ³11 mm: AUC: 0.728 Optimal threshold: 19 follicles Sensitivity: 62.3% Specificity: 75.6% PPV=6.9% Estradiol level: AUC: 0.678 Optimal threshold: 5900 pmol/L Sensitivity: 62.3% Specificity: 63.6% PPV=4.8% Both number of follicles and estradiol: sensitivity 72.5%; AUC=0.739 Severe OHSS: Number of follicles ³11 mm: AUC: 0.769 Optimal threshold: 19 follicles Sensitivity: 74.3% Specificity: 75.3% PPV=4.2% Estradiol level: AUC: 0.731 Optimal threshold: 6100 pmol/L Sensitivity: 71.4% Specificity: 64.7% PPV=2.9%
Jayaprakasan, 2009	Patients undergoing first cycle of IVF (n=118)	OHSS	Age: OR=1.093 (95%CI 0.908 to 1.315) BMI: OR=0.920 (95%CI 0.764 to 1.108) Total antral follicle count: OR=1.132 (95%CI 1.031 to 1.244) Corrected for: not reported	AUC: 0.809 Optimum cut-off value: >21 (sensitivity=83%, specificity=73%, LR+=3.1)
Jayaprakasan, 2012	1,012 consecutive subjects of all ages undergoing their first cycle of assisted reproductive techniques	Live birth & OHSS	Live birth Age: OR=0.96 (95%CI 0.93 to 0.99) AFC: OR=1.02 (95% CI 1.01 to 1.03) OHSS AFC: OR=1.03 (95%CI 1.01 to 1.05) Corrected for: not reported	Live birth AUC age: 0.58 (95%CI 0.55 to 0.62) AUC AFC: 0.59 (95%CI 0.55 to 0.63) OHSS AUC: 0.74 (95%CI 0.67 to 0.82)
Johnson, 2014	406 IVF cycles with a gonadotropin releasing hormone agonist or antagonist starting during either the preceding cycle or the stimulation cycle prior to oocyte retrieval using standard protocol and gonadotropin stimulation was carried out using follicle stimulating hormone with or without luteinizing hormone)	OHSS	Age at start (reference >30 years) ≤30 years: OR=2.46 (95%CI 1.14 to 5.34) BMI (kg/m2) (reference >30) <25: OR=2.14 (95%CI 0.68 to 6.72) 25-30: OR=1.99 (95%CI 0.64 to 5.63) Estradiol at trigger (pg/mL) (reference <3000) ³3000: OR=2.59 (95%CI 1.33 to 5.05) hCG level after trigger (IU/L) (reference <100) 100-200: OR=1.53 (95%CI 0.60 to 3.91) ³200: OR=1.42 (95%CI 0.48 to 4.20) Number of oocytes (n) (reference 1-10) 11-20: OR=6.79 (95%CI 1.97 to 23.40) >20: OR=17.55 (95%CI 4.84–63.70) Corrected for: not reported	Not reported
Kahnberg, 2009	624 consecutive patients treated with conventional IVF or intracytoplasmic sperm injection	OHSS requiring hospitalization	Variables covering oocyte aspiration Large, medium follicles: OR=1.076 (95%CI 1.01 to 1.15) Number of follicles at aspiration: OR=1.087 (95%CI 1.02 to 1.16) Number of aspirated oocytes: OR=1.109 (95%CI 1.03 to 1.19) Variables before the time point of hCG administration Large, medium follicles: OR=1.165 (95%CI 1.11 to 1.22) Corrected for: not reported	For oocyte aspiration: Optimal threshold: 25 follicles at aspiration, 19 large/medium sized follicle before hCG and 24 oocytes Sensitivity: 82.1%; Specificity: 90% PPV: 28.1%; NPV: 99.1%; LR+: 8.3 Before the time point of hCG administration: Optimal threshold: 18 medium/large sized follicles Sensitivity: 82.1%; Specificity: 79.4% PPV: 15.8%; NPV: 99%; LR+: 4.0
Kuroda, 2021	1,435,108 oocyte retrieval cycles	Incidences of moderate-to-severe OHSS	Age: OR=0.91 (0.90 to 0.91) Number of retrieved oocytes: OR=1.09 (95%CI 1.09 to 1.10) Corrected for: not reported	Not reported
Lee, 2008	262 IVF cycles stimulated with long and short GnRH agonist protocols	OHSS or clinical pregnancy	OHSS Age: OR= 0.9199 (95%CI 0.8181 to 1.0344) BMI (kg/m²): OR=0.8542 (95%CI 0.6839 to 1.0668) Basal serum AMH level: OR=1.7856 (95%CI 1.2961 to 2.4598) Serum E2 level on day of hCG administration (pg/ml): OR=1.0005 (95%CI 1.0000 to 1.0010) Number of follicles on day of hCG administration: OR=0.9808 (95%CI 0.7952 to 1.2098) Number of oocytes collected: OR=1.0657 (95%CI 0.8652 to 1.3127) Corrected for: not reported Clinical pregnancy Age: OR=0.9436 (95%CI 0.8905 to 0.9997) BMI (kg/m²): OR=0.9963 (95%CI 0.9194 to 1.0796) Basal serum AMH level: OR=1.0239 (95%CI 0.8520 to 1.2305) Serum E2 level on day of hCG administration (pg/ml): OR=1.0001 (95%CI 0.9998 to 1.0004) Number of follicles on day of hCG administration: OR=1.0456 (95%CI 0.8959 to 1.2203) Number of oocytes collected: OR= 0.9977 (95%CI 0.8598 to 1.1577) Corrected for: not reported	OHSS Age: AUC=0.710 (95%CI 0.652 to 0.763) Cut-off=33; sensitivity=76.2 (95%CI 52.8 to 91.7); specificity=56.0 (95%CI 49.5 to 62.4); PPV=13.1; NPV=96.4 BMI: AUC=0.612 (95%CI 0.551 to 0.670) Cut-off=18.44; sensitivity=33.3 (95%CI 14.6 to 57.0); specificity=90.3 (95%CI 85.8 to 93.7); PPV=23.3; NPV=93.9 Basal serum AMH level: AUC=0.902 (95%CI 0.860 to 0.934) Cut-off=3.36; sensitivity=90.5 (95%CI 69.6 to 98.5); specificity=81.3 (95%CI 75.8 to 86.0); PPV=29.7; NPV=99.0 Serum E2 level: AUC=0.811 (95%CI 0.759 to 0.856) Cut-off=1431; sensitivity=95.2 (95%CI 76.1 to 99.2); specificity=64.6 (95%CI 58.2 to 70.6); PPV=19.0; NPV=99.4 Number of follicles (³10 mm): AUC=0.846 (0.797 to 0.887) Cut-off=11; sensitivity=95.2 (95%CI 76.1 to 99.2); specificity=63.3 (95%CI 56.9 to 69.4); PPV=18.5; NPV=99.3 Number of oocytes collected: AUC=0.853 (95%CI 0.805 to 0.893) Cut-off=11; sensitivity=90.5 (95%CI 69.6 to 98.5); specificity=66.0 (95%CI 59.6 to 71.9); PPV=18.8; NPV=98.8
Lin, 2023	6931 women who had fresh embryo transfer	Severe late OHSS	Estradiol on the day of ovulation triggering (reference ≤3320.2 pg/mL) >3320.2 pg/mL: OR=2.20 (95%CI 1.03 to 4.68) Anti-Mullerian hormone (reference ≤4.62 ng/mL) >4.62 ng/mL: OR=5.44 (95%CI 2.29 to 12.90) Corrected for: not reported	Not reported
Luke, 2010	214,219 ART cycles of autologous, fresh embryo transfers to women without any treatment complications, and to those with either moderate or severe OHSS	OHSS	Any OHSS Female age (reference <30 years) 30-34 years: OR=0.71 (95%CI 0.64 to 0.80) 35-39 years: OR=0.43 (95%CI 0.38 to 0.49) ³ 40 years: OR=0.27 (95%CI 0.22 to 0.32) Severe OHSS Female age (reference <30 years) 30-34 years: OR=0.67 (95%CI 0.54 to 0.82) 35-39 years: OR=0.47 (95%CI 0.37 to 0.58) ³ 40 years: OR=0.21 (95%CI 0.15 to 0.30) Corrected for: maternal age, race and ethnicity, number of embryos transferred, and infertility diagnoses (male factor, ovulatory disorders, diminished ovarian reserve, tubal factors, uterine factors, other factors, and unexplained factors).	Not reported
Ma, 2020	300 cycles of in vitro fertilization by intracytoplasmatic sperm injection/embryo transfer (IVF-ICSI/ET)	Severe OHSS	Number of follicles on the day of hCG administration: OR=1.124 (1.027 to 1.230) Corrected for: not reported	AUC: 0.847 (95%CI 0.775 to 0.919) Optimal cut-off value of 17 (sensitivity=84.85%, specificity=77.15%)
Ni, 2022	Patients who received Long-acting GnRH agonist protocol in follicular phase for ovulation induction (n=1289)	OHSS	High level of basal antral follicles: OR=1.06 (95%CI 1.00 to 1.12) Female age: OR=0.92 (95%CI 0.83 to 1.02) Polycystic ovary syndrome: OR=2.99 (95%CI 1.00 to 8.27) High level of follicles during oocyte retrieval follicles: OR=1.09 (95%CI 1.03 to 1.14) Corrected for: not reported	AUC: 0.81
Nikbakht, 2020	Infertile and non-PCOS women with regular menstrual cycle undergoing IVF or intracytoplasmic sperm injection (n=144)	OHSS	BMI: OR=1.434, 95%CI 1.070 to 1.921 Number of preovulatory follicles: OR=1.539 (95%CI 1.147 to 2.063) Corrected for: not reported	Optimal cut-off for preovulatory follicles: 10 (AUC=0.86, sensitivity=80%, specificity=88%)
Schirmer, 2020	All fresh cycles (autologous and donor) and embryo-banking cycles (n = 1,833,430 cycles)	OHSS	Fresh autologous cycles in which embryo transfer occurred Age (reference ³41): <30 years: RR=2.27 (95%CI 1.76 to 2.92) 30-34 years: RR=2.02 (95%CI 1.58 to 2.59) 35-37 years: RR=1.79 (95%CI 1.39 to 2.31) 38-40 years: RR=1.49 (95%CI 1.14 to 1.94) BMI (reference 18.5 to 24.9): <18.5 kg/m2: RR=0.95 (95%CI 0.74 to 1.21) 25.0 to 29.9 kg/m2: RR=0.82 (95%CI 0.75 to 0.90) ³30.0 kg/m2: RR=0.66 (95%CI 0.59 to 0.74) Number of oocytes retrieved (reference 11-15): 0-10 oocytes: RR=0.37 (0.32 to 0.42) 16-30 oocytes: RR=1.90 (1.73 to 2.08) >30 oocytes: RR=3.85 (3.36 to 4.41) Fresh autologous cycles and embryo-banking cycles Age (reference ³41): <30 years: RR=6.47 (5.46 to 7.66) 30-34 years: RR=4.97 (4.22 to 5.86) 35-37 years: RR=3.43 (2.89 to 4.06) 38-40 years: RR=2.12 (1.77 to 2.54) BMI (reference 18.5 to 24.9): <18.5 kg/m2: RR=0.99 (95%CI 0.85 to 1.15) 25.0 to 29.9 kg/m2: RR=0.86 (95%CI 0.80 to 0.92) ³30.0 kg/m2: RR=0.70 (95%CI 0.65 to 0.76) Corrected for age, race, body mass index, previous pregnancy, current pregnancy, diagnosis of ovulatory disorder, uterine factor, tubal factor, endometriosis, diminished ovarian reserve, unexplained infertility, number of oocytes retrieved, GnRH antagonist use for pituitary suppression, and embryo-banking cycle.	Not reported
Shields, 2016 case-control study	Women undergoing IVF treatment through Monash IVF with OHSS as cases (n=162) and who did not have OHSS as controls (n=3756)	OHSS	Age: IRR=0.60 (95%CI 0.52 to 0.69) BMI (kg/m2): IRR=1.10 (95%CI 0.96 to 1.26 Max E2 concentration: IRR=1.43 (95%CI 1.31 to 1.57) Number of follicles: IRR=1.40 (95%CI 1.29 to 1.52) Corrected for: not reported	ROC area: 0.846 (95%CI 0.816 to 0.876) Sensitivity: 81.7% (74.3 to 87.7%) Specificity: 75.6% (74.2 to 77.0%)
Steward, 2014	256,381 fresh autologous in vitro fertilization (IVF) cycles	Live birth & OHSS	Live birth (reference group of 11-15 retrieved oocytes) 0-5 oocytes: OR=0.46 (95% CI 0.44 to 0.48) 6-10 oocytes: OR=0.83 (95% CI 0.80 to 0.85) 16-20 oocytes: OR=1.06 (95% CI 1.03 to 1.1) 21-25 oocytes: OR=1.04 (95% CI 1 to 1.08) >25 oocytes: OR=0.91 (95% CI 0.87 to 0.95) OHSS (reference group of 11-15 retrieved oocytes) 0-5 oocytes: OR=0.09 (95%CI 0.05 to 0.15) 6-10 oocytes: OR=0.39 (95%CI 0.32to 0.47) 16-20 oocytes: OR=1.62 (95% CI 1.41 to 1.86) 21-25 oocytes: OR=2.93 (95% CI 2.55 to 3.36) >25 oocytes: OR=6.16 (95% CI 5.44 to 6.98) Corrected for: age, BMI, basal FSH, and smoking status	Optimal cut-off point for OHSS: 15 oocytes (sensitivity=71.1%, specificity=72.4%) AUC=0.784. Live birth AUC=0.596
Tarlatzis, 2017	All fresh IVF cycles with ovarian stimulation performed with gonadotrophins and GnRH agonists or antagonists and triggering of final oocyte maturation was induced with the administration of urinary or recombinant hCG (2982 patients undergoing 5493 cycles)	Moderate or severe OHSS	Severe OHSS Single predictors: Number of follicles ³10 mm: OR=1.18 (95%CI 1.13 to 1.23) E2 on the day of hCG: OR=2.80 (95%CI 1.80 to 4.37) Follicles and E2 on the day of hCG and total FSH dose model: Number of follicles ³10 mm: OR=1.12 (95%CI 1.05 to 1.20) E2 on the day of hCG (per 1000 pg/mL): OR=1.89 (95%CI 0.93 to 3.83) Corrected for: not reported Serum anti-mullerian hormone: OR=0.90 (95%CI 0.74 to 1.08) Corrected for: number of follicles ≥10 mm on the day of hCG trigger PCOS: OR=1.63 (95%CI 0.27 to 9.99) Corrected for: total number of follicles ≥10 mm Moderate OHSS Single predictors: Number of follicles ³10 mm: OR=1.14 (95%CI 1.11 to 1.17) E2 on the day of hCG (per 1000 pg/mL): OR=1.80 (95%CI 1.50 to 2.15) Follicles and E2 on the day of hCG and total FSH dose model: Number of follicles ³10 mm: OR=1.12 (95%CI 1.08 to 1.16) E2 on the day of hCG (per 1000 pg/mL): OR=1.16 (95%CI 0.88 to 1.52) Corrected for: not reported	Severe OHSS Single predictors: Number of follicles ³10 mm AUC=0.904 (95%CI 0.895 to 0.912) Cut-off: ≥15; sensitivity=89.5 (95%CI 74.0 to 99.0); specificity=82.9 (80.6 to 82.7); PLR=5.19; NLR=0.13 Single predictors: E2 on day of hCG AUC= 0.790 (95%CI 0.779 to 0.801) Cut-off: ≥2.201; sensitivity=85.0 (95%CI 62.1 to 96.8); specificity=71.8 (95%CI 70.5 to 72.9); PLR=3.01; NLR=0.21 Number of follicles and E2 on the day of hCG and total FSH dose model: AUC=0.916 (0.908–0.923) Cut-off= >0.0054; sensitivity=84.2(95%CI 60.4 to 96.6); specificity=85.9 (95%CI 84.9 to 86.9); PLR=5.98; NLR=0.18 Moderate OHSS Single predictors: Number of follicles ³10 mm AUC=0.787 (95%CI 0.775 to 0.798) Cut-off: ≥12; sensitivity=74.7 (95%CI 62.9 to 84.2); specificity=70.4 (69.1 to 71.6); PLR=2.52; NLR=0.36 Single predictor E2 on day of hCG: AUC=0.691 (95%CI 0.678 to 0.703); Cut-off=≥1.540; sensitivity=85.1 (95%CI 75.0 to 92.3); specificity=47.4 (95%CI 46.0 to 48.7); PLR=1.62; NLR=0.31 Number of follicles and E2 on the day of hCG and total FSH dose model: AUC=0.796 (95%CI 0.785 to 0.807) Cut-off=>0.0127; sensitivity=80.3 (95%CI 69.1 to 88.8); specificity=69.7 (95%CI 68.4 to 70.9); PLR=2.65; NLR=0.28
Xu, 2021 case-control study	Total of 21,222 ovarian stimulation cycles were collected among women undergoing assisted reproductive technology, among which 84 patients with late-onset OHSS and control cases were the remaining 21,138	OHSS	Estradiol level on hCG triggering ovulation: OR=1.0000 (95%CI 1.0000 to 1.0001) Corrected for: not reported	Not reported

_{Abbreviations: NPCOS=non-polycystic ovary syndrome; LR+=positive likelihood ratio; PPV=positive predictive value; NPV=negative predictive value; PLR=positive likelihood ratio; NLR=negative likelihood ratio}

Referenties

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Aramwit P, Pruksananonda K, Kasettratat N, Jammeechai K. Risk factors for ovarian hyperstimulation syndrome in Thai patients using gonadotropins for in vitro fertilization. Am J Health Syst Pharm. 2008 Jun 15;65(12):1148-53. doi: 10.2146/ajhp070566. PMID: 18541685.
Ashrafi M, Bahmanabadi A, Akhond MR, Arabipoor A. Predictive factors of early moderate/severe ovarian hyperstimulation syndrome in non-polycystic ovarian syndrome patients: a statistical model. Arch Gynecol Obstet. 2015 Nov;292(5):1145-52. doi: 10.1007/s00404-015-3723-0. Epub 2015 Apr 29. PMID: 25920524.
Griesinger G, Verweij PJ, Gates D, Devroey P, Gordon K, Stegmann BJ, Tarlatzis BC. Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol. PLoS One. 2016 Mar 7;11(3):e0149615. doi: 10.1371/journal.pone.0149615. PMID: 26950065; PMCID: PMC4780699.
Jayaprakasan K, Jayaprakasan R, Al-Hasie HA, Clewes JS, Campbell BK, Johnson IR, Raine-Fenning NJ. Can quantitative three-dimensional power Doppler angiography be used to predict ovarian hyperstimulation syndrome? Ultrasound Obstet Gynecol. 2009 May;33(5):583-91. doi: 10.1002/uog.6373. Erratum in: Ultrasound Obstet Gynecol. 2009 Oct;34(4):489. PMID: 19402100.
Jayaprakasan K, Chan Y, Islam R, Haoula Z, Hopkisson J, Coomarasamy A, Raine-Fenning N. Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women. Fertil Steril. 2012 Sep;98(3):657-63. doi: 10.1016/j.fertnstert.2012.05.042. Epub 2012 Jun 29. PMID: 22749225.
Kahnberg A, Enskog A, Brännström M, Lundin K, Bergh C. Prediction of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Acta Obstet Gynecol Scand. 2009;88(12):1373-81. doi: 10.3109/00016340903287482. PMID: 19878052.
Johnson MD, Williams SL, Seager CK, Liu JH, Barker NM, Hurd WW. Relationship between human chorionic gonadotropin serum levels and the risk of ovarian hyperstimulation syndrome. Gynecol Endocrinol. 2014 Apr;30(4):294-7. doi: 10.3109/09513590.2013.875998. Epub 2014 Jan 23. PMID: 24455971.
Kuroda K, Nagai S, Ikemoto Y, Matsumura Y, Ochiai A, Nojiri S, Itakura A, Sugiyama R. Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals. Reprod Biomed Online. 2021 Jan;42(1):125-132. doi: 10.1016/j.rbmo.2020.09.001. Epub 2020 Sep 3. PMID: 33051135.
Lee TH, Liu CH, Huang CC, Wu YL, Shih YT, Ho HN, Yang YS, Lee MS. Serum anti-Müllerian hormone and estradiol levels as predictors of ovarian hyperstimulation syndrome in assisted reproduction technology cycles. Hum Reprod. 2008 Jan;23(1):160-7. doi: 10.1093/humrep/dem254. Epub 2007 Nov 13. PMID: 18000172.
Lin L, Yuan X, Li X, Hunt S, Chen G, Luo S. Determinants of Severe Late Ovarian Hyperstimulation Syndrome in Fresh Embryo Transfer Cycles Based on Integration of Decision Tree Classification and Conditional Logistic Regression. Clinical and Experimental Obstetrics & Gynecology. 2023;50(2),36.
Luke B, Brown MB, Morbeck DE, Hudson SB, Coddington CC 3rd, Stern JE. Factors associated with ovarian hyperstimulation syndrome (OHSS) and its effect on assisted reproductive technology (ART) treatment and outcome. Fertil Steril. 2010 Sep;94(4):1399-1404. doi: 10.1016/j.fertnstert.2009.05.092. Epub 2009 Jul 9. PMID: 19591989.
Ma T, Niu Y, Wei B, Xu L, Zou L, Che X, Wang X, Tang D, Huang R, Chen B. Moderate-to-severe ovarian hyperstimulation syndrome: A retrospective multivariate logistic regression analysis in Chinese patients. Adv Clin Exp Med. 2020 Jan;29(1):85-90. doi: 10.17219/acem/92916. PMID: 31990458.
Ni YH, Zhang HL, Jiang WW. Analysis and prediction of risk factors of ovarian hyperstimulation caused by Long-acting GnRH agonist protocol in follicular phase. Eur Rev Med Pharmacol Sci. 2022 May;26(9):3261-3268. doi: 10.26355/eurrev_202205_28744. PMID: 35587077.
Nikbakht R, Zargar M, Moramezi F, Ziafat M, Tabesh H, Sattari AR, Sattari SA. Insulin Resistance and Free Androgen as Predictors for Ovarian Hyperstimulation Syndrome in Non-PCOS Women. Horm Metab Res. 2020 Feb;52(2):104-108. doi: 10.1055/a-1079-5342. Epub 2020 Jan 23. PMID: 31975364.
Oudshoorn SC, van Tilborg TC, Eijkemans MJC, Oosterhuis GJE, Friederich J, van Hooff MHA, van Santbrink EJP, Brinkhuis EA, Smeenk JMJ, Kwee J, de Koning CH, Groen H, Lambalk CB, Mol BWJ, Broekmans FJM, Torrance HL; OPTIMIST study group. Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder. Hum Reprod. 2017 Dec 1;32(12):2506-2514. doi: 10.1093/humrep/dex319. PMID: 29121269.
Schirmer DA 3rd, Kulkarni AD, Zhang Y, Kawwass JF, Boulet SL, Kissin DM. Ovarian hyperstimulation syndrome after assisted reproductive technologies: trends, predictors, and pregnancy outcomes. Fertil Steril. 2020 Sep;114(3):567-578. doi: 10.1016/j.fertnstert.2020.04.004. Epub 2020 Jul 14. PMID: 32680613; PMCID: PMC8041489.
Selter J, Wen T, Palmerola KL, Friedman AM, Williams Z, Forman EJ. Life-threatening complications among women with severe ovarian hyperstimulation syndrome. Am J Obstet Gynecol. 2019 Jun;220(6):575.e1-575.e11. doi: 10.1016/j.ajog.2019.02.009. Epub 2019 Feb 8. PMID: 30742828.
Shields R, Vollenhoven B, Ahuja K, Talmor A. Ovarian hyperstimulation syndrome: A case control study investigating risk factors. Aust N Z J Obstet Gynaecol. 2016 Dec;56(6):624-627. doi: 10.1111/ajo.12515. Epub 2016 Aug 17. PMID: 27531056.
Steward RG, Lan L, Shah AA, Yeh JS, Price TM, Goldfarb JM, Muasher SJ. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril. 2014 Apr;101(4):967-73. doi: 10.1016/j.fertnstert.2013.12.026. Epub 2014 Jan 23. PMID: 24462057.
Tarlatzi TB, Venetis CA, Devreker F, Englert Y, Delbaere A. What is the best predictor of severe ovarian hyperstimulation syndrome in IVF? A cohort study. J Assist Reprod Genet. 2017 Oct;34(10):1341-1351. doi: 10.1007/s10815-017-0990-7. Epub 2017 Jul 14. PMID: 28710674; PMCID: PMC5633577.
Xu H, Yang S, Cui L, Feng G, Li R, Qiao J. Investigation on the risk factors for late-onset OHSS: a retrospective case-control study. Arch Gynecol Obstet. 2022 Mar;305(3):731-736. doi: 10.1007/s00404-021-06182-9. Epub 2021 Aug 19. PMID: 34410473.
Youssef MA, Van der Veen F, Al-Inany HG, Mochtar MH, Griesinger G, Nagi Mohesen M, Aboulfoutouh I, van Wely M. Gonadotropin-releasing hormone agonist versus HCG for oocyte triggering in antagonist-assisted reproductive technology. Cochrane Database Syst Rev. 2014 Oct 31;2014(10):CD008046. doi: 10.1002/14651858.CD008046.pub4. PMID: 25358904; PMCID: PMC10767297.

Evidence tabellen

Since no internal or external validation was performed in these studies, no evidence table or risk of bias table were provided, but only descriptive data were presented.

Table of excluded studies

Reference	Reason for exclusion
Aflatoonian A, Oskouian H, Ahmadi S, Oskouian L. Prediction of high ovarian response to controlled ovarian hyperstimulation: anti-Müllerian hormone versus small antral follicle count (2-6 mm). J Assist Reprod Genet. 2009 Jun;26(6):319-25. doi: 10.1007/s10815-009-9319-5. Epub 2009 Jun 20. PMID: 19543966; PMCID: PMC2729857.	Wrong outcome: high ovarian response
Alhilali MJ, Parham A, Attaranzadeh A, Amirian M, Azizzadeh M. Polycystic Ovary Syndrome Develops the Complications of Assisted Reproductive Technologies. Arch Razi Inst. 2022 Aug 31;77(4):1459-1464. doi: 10.22092/ARI.2022.358889.2329. PMID: 36883162; PMCID: PMC9985778.	No multivariable model
Anckaert E, Denk B, He Y, Torrance HL, Broekmans F, Hund M. Evaluation of the Elecsys® anti-Müllerian hormone assay for the prediction of hyper-response to controlled ovarian stimulation with a gonadotrophin-releasing hormone antagonist protocol. Eur J Obstet Gynecol Reprod Biol. 2019 May;236:133-138. doi: 10.1016/j.ejogrb.2019.02.022. Epub 2019 Mar 2. PMID: 30909009.	No multivariable model
Bhakta R, KUMAR ADIGA PK. Predicting the Ovarian Response in ART Cycles Using Rate of Increase in Serum Estradiol on Day Six of Controlled Ovarian Hyperstimulation. J Turkish-German Gynecol Assoc. 2006 Sep;7(3).	No multivariable model
Broer SL, Dólleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Hum Reprod Update. 2011 Jan-Feb;17(1):46-54. doi: 10.1093/humupd/dmq034. Epub 2010 Jul 28. PMID: 20667894.	Wrong outcome: not only OHSS; also other excessive ovarian response
Broer SL, Dólleman M, van Disseldorp J, Broeze KA, Opmeer BC, Bossuyt PM, Eijkemans MJ, Mol BW, Broekmans FJ; IPD-EXPORT Study Group. Prediction of an excessive response in in vitro fertilization from patient characteristics and ovarian reserve tests and comparison in subgroups: an individual patient data meta-analysis. Fertil Steril. 2013 Aug;100(2):420-9.e7. doi: 10.1016/j.fertnstert.2013.04.024. Epub 2013 May 28. PMID: 23721718.	No OHSS; also other excessive ovarian response
Checa MA, Prat M, Carreras R. Antral follicle count as a predictor of hyperresponse in controlled ovarian hyperstimulation/intrauterine insemination in unexplained sterility. Fertil Steril. 2010 Aug;94(3):1105-7. doi: 10.1016/j.fertnstert.2009.10.063. Epub 2010 Jan 4. PMID: 20045519.	Wrong outcome: predictors for cancellation of a cycle in COH/IUI due hyperresponse
Hudeck R, Ventruba P, Unzeitig V, Vavruskova R, Racanska E, Sarmanova, J. Analysis of ovarian hyperstimulation syndrome development using data mining. Scripta Medica. 2005 Dec;78(6):329-340	No multivariate model; only risk factors described, no raw data presented (data mining)
Jayaprakasan K, Herbert M, Moody E, Stewart JA, Murdoch AP. Estimating the risks of ovarian hyperstimulation syndrome (OHSS): implications for egg donation for research. Hum Fertil (Camb). 2007 Sep;10(3):183-7. doi: 10.1080/14647270601021743. PMID: 17786651.	No multivariate model; only percentage for risk of getting OHSS presented
La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010 Mar-Apr;16(2):113-30. doi: 10.1093/humupd/dmp036. Epub 2009 Sep 30. PMID: 19793843.	No multivariable model
Leijdekkers JA, van Tilborg TC, Torrance HL, Oudshoorn SC, Brinkhuis EA, Koks CAM, Lambalk CB, de Bruin JP, Fleischer K, Mochtar MH, Kuchenbecker WKH, Laven JSE, Mol BWJ, Broekmans FJM, Eijkemans MJC; OPTIMIST study group. Do female age and body weight modify the effect of individualized FSH dosing in IVF/ICSI treatment? A secondary analysis of the OPTIMIST trial. Acta Obstet Gynecol Scand. 2019 Oct;98(10):1332-1340. doi: 10.1111/aogs.13664. Epub 2019 Jun 21. PMID: 31127607.	Wrong outcome: OHSS risks defined as any form of OHSS and/or preventive interventions (cancellation or freeze-all strategy)
Luo XZ, Chen HM, Jiang HY, Zhu J. Risk factors, clinical manifestation and therapy strategy for ovarian hyperstimulation syndrome-a retrospective study of 358 patients. Int J Clin Exp Med. 2016 Jan 1;9(3):6777-82.	Wrong outcome: recovery time, duration of hospitalization and severity of OHSS
Marzuki VA, Faizah Z, Aswin RH, Sa’adi A. Predictive Factors Associated with Ovarian Hyperstimulation Syndrome in Indonesian Women Undergoing IVF. Indian Journal of Public Health Research & Development. 2021 Apr 1;12(2).	No multivariable model
Madrazo I, Vélez MF, Hidalgo JJ, Ortiz G, Suárez JJ, Porchia LM, Gonzalez-Mejia ME, López-Bayghen E. Prediction of severe ovarian hyperstimulation syndrome in women undergoing in vitro fertilization using estradiol levels, collected ova, and number of follicles. J Int Med Res. 2020 Aug;48(8):300060520945551. doi: 10.1177/0300060520945551. PMID: 32790579; PMCID: PMC7427026.	No multivariable model
Michaelson-Cohen R, Altarescu G, Beller U, Reens R, Halevy-Shalem T, Eldar-Geva T. Does elevated human chorionic gonadotropin alone trigger spontaneous ovarian hyperstimulation syndrome? Fertil Steril. 2008 Nov;90(5):1869-74. doi: 10.1016/j.fertnstert.2007.09.049. Epub 2007 Dec 31. PMID: 18166181.	Only descriptive data
Mocanu E, Redmond ML, Hennelly B, Collins C, Harrison R. Odds of ovarian hyperstimulation syndrome (OHSS) - time for reassessment. Hum Fertil (Camb). 2007 Sep;10(3):175-81. doi: 10.1080/14647270701194143. PMID: 17786650.	No multivariate model; OR for being admitted for OHSS by E2 level and oocyte number
Mubarak AM, Jarrah DM, Farhood MK, Abas NF, Yousif MG. Use of stimulated day 5 estradiol levels in a treatment cycle for the prediction of ovarian response in in vitro fertilization. Drug Invention Today. 2019 Oct 15;12(10).	Wrong outcome: multivariable model not specific for OHSS
Nastri CO, Teixeira DM, Moroni RM, Leitão VM, Martins WP. Ovarian hyperstimulation syndrome: pathophysiology, staging, prediction and prevention. Ultrasound Obstet Gynecol. 2015 Apr;45(4):377-93. doi: 10.1002/uog.14684. Epub 2015 Mar 1. PMID: 25302750.	No multivariable model
Neves AR, Blockeel C, Griesinger G, Garcia-Velasco JA, Marca A, Rodriguez I, Drakopoulos P, Alvarez M, Tournaye H, Polyzos NP. The performance of the Elecsys® anti-Müllerian hormone assay in predicting extremes of ovarian response to corifollitropin alfa. Reprod Biomed Online. 2020 Jul;41(1):29-36. doi: 10.1016/j.rbmo.2020.03.023. Epub 2020 Apr 30. PMID: 32466992.	Wrong outcome: excessive ovarian response
Ocal P, Sahmay S, Cetin M, Irez T, Guralp O, Cepni I. Serum anti-Müllerian hormone and antral follicle count as predictive markers of OHSS in ART cycles. J Assist Reprod Genet. 2011 Dec;28(12):1197-203. doi: 10.1007/s10815-011-9627-4. Epub 2011 Sep 1. PMID: 21882017; PMCID: PMC3241835.	No multivariable model
Pakhomov SP, Orlova VS, Verzilina IN, Sukhih NV, Nagorniy AV, Matrosova AV. Risk Factors and Methods for Predicting Ovarian Hyperstimulation Syndrome (OHSS) in the in vitro Fertilization. Arch Razi Inst. 2021 Nov 30;76(5):1461-1468. doi: 10.22092/ari.2021.355581.1700. PMID: 35355759; PMCID: PMC8934082.	No multivariable model
Peluso C, Fonseca FL, Gastaldo GG, Christofolini DM, Cordts EB, Barbosa CP, Bianco B. AMH and AMHR2 polymorphisms and AMH serum level can predict assisted reproduction outcomes: a cross-sectional study. Cell Physiol Biochem. 2015;35(4):1401-12. doi: 10.1159/000373961. Epub 2015 Mar 12. PMID: 25790842.	No suitable outcomes
Rajesh H, Lee WY, Fook-Chong S, Yu SL. Ovarian hyperstimulation syndrome: an analysis of patient characteristics in the Asian population. Singapore Med J. 2011 Mar;52(3):168-74. PMID: 21451925.	No multivariable model
Salmassi A, Mettler L, Hedderich J, Jonat W, Deenadayal A, von Otte S, Eckmann-Scholz C, Schmutzler AG. Cut-Off Levels of Anti-Mullerian Hormone for The Prediction of Ovarian Response, In Vitro Fertilization Outcome and Ovarian Hyperstimulation Syndrome. Int J Fertil Steril. 2015 Jul-Sep;9(2):157-67. doi: 10.22074/ijfs.2015.4236. Epub 2015 Jul 27. PMID: 26246873; PMCID: PMC4518483.	No multivariable model
Selter J, Wen T, Palmerola KL, Friedman AM, Williams Z, Forman EJ. Life-threatening complications among women with severe ovarian hyperstimulation syndrome. Am J Obstet Gynecol. 2019 Jun;220(6):575.e1-575.e11. doi: 10.1016/j.ajog.2019.02.009. Epub 2019 Feb 8. PMID: 30742828.	Wrong population: hospital admission for OHSS
Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Ross R, Morris S. Effects of the ovulatory serum concentration of human chorionic gonadotropin on the incidence of ovarian hyperstimulation syndrome and success rates for in vitro fertilization. Fertil Steril. 2005 Jul;84(1):93-8. doi: 10.1016/j.fertnstert.2004.12.053. PMID: 16009163.	No multivariate model (logistic regression); only risk factors described, no raw data (e.g. OR)
Sood A, Goel A, Boda S, Mathur R. Prediction of significant OHSS by ovarian reserve and ovarian response - implications for elective freeze-all strategy. Hum Fertil (Camb). 2022 Apr;25(2):390-396. doi: 10.1080/14647273.2020.1809021. Epub 2020 Aug 24. PMID: 32835544.	No multivariable model
Sousa M, Cunha M, Teixeira da Silva J, Oliveira C, Silva J, Viana P, Barros A. Ovarian hyperstimulation syndrome: a clinical report on 4894 consecutive ART treatment cycles. Reprod Biol Endocrinol. 2015 Jun 23;13:66. doi: 10.1186/s12958-015-0067-3. PMID: 26100393; PMCID: PMC4477314.	No multivariable model
Swanton A, Story L, McVeigh E, Child T. IVF outcome in women with PCOS, PCO and normal ovarian morphology. Eur J Obstet Gynecol Reprod Biol. 2010 Mar;149(1):68-71. doi: 10.1016/j.ejogrb.2009.11.017. Epub 2009 Dec 22. PMID: 20022685.	No multivariable model; no raw data
Tummon I, Gavrilova-Jordan L, Allemand MC, Session D. Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review*. Acta Obstet Gynecol Scand. 2005 Jul;84(7):611-6. doi: 10.1111/j.0001-6349.2005.00788.x. PMID: 15954867.	No multivariable model
Verwoerd GR, Mathews T, Brinsden PR. Optimal follicle and oocyte numbers for cryopreservation of all embryos in IVF cycles at risk of OHSS. Reprod Biomed Online. 2008 Sep;17(3):312-7. doi: 10.1016/s1472-6483(10)60213-1. PMID: 18765000.	No multivariable model
Wei J, Xiong D, Zhang Y, Zeng J, Liu W, Ye F. Predicting ovarian responses to the controlled ovarian hyperstimulation in elderly infertile women using clinical measurements and random forest regression. Eur J Obstet Gynecol Reprod Biol. 2023 Sep;288:153-159. doi: 10.1016/j.ejogrb.2023.07.012. Epub 2023 Jul 24. PMID: 37544248.	Wrong outcome: number of oocytes retrieved

Verantwoording

Beoordelingsdatum en geldigheid

Publicatiedatum : 02-01-2026

Beoordeeld op geldigheid : 02-01-2026

Initiatief en autorisatie

Initiatief:

Nederlandse Vereniging voor Obstetrie en Gynaecologie

Geautoriseerd door:

Nederlandse Vereniging voor Obstetrie en Gynaecologie
Patiëntenfederatie Nederland
Freya
Vereniging voor Fertiliteitsartsen

Algemene gegevens

De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd door de Stichting Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodule is in 2022 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met OHSS.

Werkgroep

Dr. G. (Gijs) Teklenburg (voorzitter)(NVOG)
Dr. A. (Arno) van Peperstraten (NVOG)
Prof. dr. F. (Frank) Broekmans (NVOG)
Drs. E. (Eefje) Oude Lohuis (NVOG)
Dr. S. (Sanne) Braam (NVOG)
Dr. L. (Leonie) van Houten (NVOG)
Drs. H.G.I. (Hans) van Weering (NVOG)
Dr. M. (Mèlanie) van IJsselmuiden (NVOG)
Dr. S. (Sietske) Gaykema (NVOG)
Dr. L. (Lotte) Weimar (NVOG)
Dr. A. (Annelien) de Kat (NVOG)
Drs. E.C.G. (Esther) van Duinen (VVF)
Drs. M. (Marloes) Vermeulen (FREYA) (tot november 2024)
Simone Sinjorgo (FREYA) (van december 2024)

Met ondersteuning van

Dr. M. (Mohammadreza) Abdollahi, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Dr. I.M. (Irina) Mostovaya, senior adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Dr. Y.J. (Yvonne) Labeur, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Dr. J. (Jana) Tuijtelaars, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Drs. D.A.M. (Danique) Middelhuis, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Dr. M. (Majke) van Bommel, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Dr. T. (Tiny) Hoekstra, senior adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Dr. L. (Leanne) Küpers, adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Drs. T. (Thibaut) Dederen, junior adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Drs. D.A.M. (Fieke) Pepping, junior adviseur, Kennisinstituut van de Federatie van Medisch Specialisten
Alies van der Wal, medisch informatie specialist, Kennisinstituut van de Federatie Medisch Specialisten
Esther van der Bijl, medisch informatie specialist, Kennisinstituut van de Federatie Medisch Specialisten

Belangenverklaringen

Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.

Naam	Hoofdfunctie	Nevenwerkzaamheden	Persoonlijke financiële belangen	Persoonlijke relaties	Extern gefinancierd onderzoek	Intellectuele belangen en reputatie	Overige belangen	Datum	Restrictie
Gijs Teklenburg	Gynaecoloog, subspecialist voortplantings geneeskunde.	Medical advisor Gedeon Richter Medical advisor Merck	Geen	Geen	Geen	Geen	Geen	02/05/2025
Annelien de Kat	Gynaecoloog Amsterdam UMC	Geen	Geen	Geen	Geen onderzoeksgelden <3 jaar geleden ontvangen (in 2017 wetenschapsbeurs van de KNAW).	Geen	Geen	29/04/2025
Arno van Peperstraten	Gynaecoloog bij UMC Utrecht	Geen	Laatste drie jaar enkele keren vergoeding gastvrijheid ontvangen (Merck en Ferring), onkosten (Merck) en ook dienstverlening honorarium (Merck).	Geen	Geen	Geen	Geen	09/05/2025
Frank Broekmans	Hoogleraar Voortplantingsgeneeskunde, UMC Utrecht Gynaecoloog, Centrum voor Kinderwens, Dijklander ziekenhuis, Purmerend	Onderwijs en advies via: FrankSchoolRforL Education - Consultation - Coaching In Human Reproductive Medicine Research manager Stichting Long Covid Waarnemend voorzitter Promoties Geneeskunde Universiteit Utrecht	lid adviesraad Merck B.V. lid adviesraad Ferring B.V. Lid adviesraad Abbott Lid adviesraad Besins	Geen	Geen	Geen	Geen	30/04/2025
Eefje Oude Lohuis	Gynaecoloog, subspecialist voortplantingsgeneeskunde, Haaglanden Medisch Centrum Den Haag	Geen	Geen	Geen	Geen	Geen	Geen	13/05/2025
Sanne Braam	lid werkgroep, NVOG, onbetaald.	Geen	Geen	Geen	Geen	Geen	Geen	29/04/2025
Leonie van Houten	Gynaecoloog Amphia Ziekenhuis Breda subspecialist VPG Amphia Ziekenhuis Breda.	Geen	Geen	Geen	Geen	Geen	Geen	06/05/2025
Hans van Weering	Gynaecoloog, subspecialist voortplantingsgeneeskunde.Rode Kruisziekenhuis BV, Beverwijk, thans WHC Amsterdam	Geen	Geen	Geen	Scratch OFO trial	Geen	Deels door Merck vergoede congresreis ESHRE 2019, 2022 en LH symposium 2022 (conform CGR) Deelname aan Merck Business Academy	26/04/2025
Charlotte Weimar	Gynaecoloog, Werkgever: UMC Utrecht	Geen	Geen	Geen	Geen	Geen	Niet bij mij bekend. Enige nog te noemen is mijn deelname (dec 2022) aan de ESHRE campus course ("Implantation failure, recurrent pregnancy loss and endometrial disorders" ) omdat die reis deels gefinancierd werd door Ferring BV.	12/05/2025
Mèlanie van IJsselmuiden	Gynaecoloog, Isala Zwolle	Geen	Geen	Geen	Ik heb van enkele farmaceuten een kleine financiële bijdrage gekregen voor het drukken van mijn proefschrift in de zomer van 2020 (niet gerelateerd aan OHSS)	Geen	Geen	13/05/2025
Sietske Gaykema	Treant zorggroep gynaecoloog	Commissie onderwijs nvog	Geen	Geen	Geen	Geen	Geen	05/05/2025
Esther van Duinen	Fertiliteitsarts, 36 uur per week. Betaald. Sint Antonius Ziekenhuis.	Voorzitter van VVF (Vereniging van Fertiliteitsartsen). Niet betaald.	Geen financieel voordeel derhalve ik zelf niets te maken heb met de financiën van mijn praktiserend instituut (het ziekenhuis) of mijn afdeling.	Geen	Geen	Geen	Geen	28/04/2025
Marloes Vermeulen (tot november 2024)	Freya, medewerker externe relaties	Verloskundige 1e lijn.	Geen	Geen	Geen	Geen.	Geen.	27/09/2022
Simone Sinjorgo	Parttime medewerker patiëntenperspectief bij Freya (14 uur, betaald). Betrokken bij richtlijnontwikkeling en onderzoek op het gebied van fertiliteit (OFO, OHSS, mannelijke subfertiliteit) ter vertegenwoordiging van het patiëntenperspectief.	Lichaamsgericht psychosociaal therapeut (zzp, eigen praktijk in Dongen-Vaart, geregistreerd bij RBCZ). Daarnaast docent psychosociale bijscholing voor therapeuten en vrouwencoach-opleiding (betalingen via eigen praktijk)	Geen	Geen	Geen	Geen	Geen	27/04/2025

Inbreng patiëntenperspectief

De werkgroep besteedde aandacht aan het patiëntenperspectief door de Patiëntenfederatie Nederland en FREYA uit te nodigen voor de schriftelijke knelpunteninventarisatie, en door deelname van een afgevaardigde van FREYA in de werkgroep. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De richtlijn is tevens voor commentaar voorgelegd aan Patientfederatie Nederland en FREYA en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.

Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz

Bij de richtlijnmodule voerde de werkgroep conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uit om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema bij Werkwijze).

Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn, zie onderstaande tabel.

Module	Uitkomst raming	Toelichting
Predisponerende factoren van OHSS	geen financiële gevolgen	Het betreft hier 5.000-40.000 patienten, waarbij kan worden gesteld dat het overgrote deel van de zorgaanbieders al voldoet aan de norm.

Werkwijze

Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.

Zoekverantwoording

Algemene informatie

Cluster/richtlijn: NVOG Modulaire actualisatie richtlijn Ovarieel Hyperstimulatiesyndroom (OHSS)
Uitgangsvraag/modules: Wat zijn de predisponerende factoren van OHSS?
Database(s): Embase.com, Ovid/Medline	Datum: 10 oktober 2023
Periode: vanaf 2000	Talen: geen restrictie
Literatuurspecialist: Alies van der Wal	Rayyan review: https://rayyan.ai/reviews/804060
BMI-zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ Bij gebruikmaking van een volledig zoekblok zal naar de betreffende link op de website worden verwezen.
Toelichting: Voor deze vraag is gezocht op de elementen: IVF/ ICSI/ eicelvitrificatie Ovarieel hyperstimulatiesyndroom Prognostisch filter →De sleutelartikelen worden gevonden met deze search →Het prognostisch filter is aangevuld met een zoekblok over risk assessment
Te gebruiken voor richtlijntekst: In de databases Embase.com en Ovid/Medline is op 10 oktober 2023 systematisch gezocht naar studies over predisponerende factoren van ovarieel hyperstimulatiesyndroom. De literatuurzoekactie leverde 1001 unieke treffers op.

Zoekopbrengst

	EMBASE	OVID/MEDLINE	Ontdubbeld
SR	156	69	174
Observationele studies	742	403	827
Overig	326	235	383
Totaal	1224	707	1001*

_{*in Rayyan}

Zoekstrategie

Embase.com

No.	Query	Results
#1	'in vitro fertilization'/exp OR ((('in vitro' OR extracorporeal) NEAR/3 (fertilisation OR fertilization)):ti,ab,kw) OR ivf:ti,ab,kw OR 'intracytoplasmic sperm injection'/exp OR 'intracytoplasmic sperm injection':ti,ab,kw OR 'intra cytoplasmic sperm injection':ti,ab,kw OR icsi:ti,ab,kw OR 'ovulation induction'/exp OR (((ovar* OR ovulation) NEAR/3 (stimulation OR hyperstimulation OR induc)):ti,ab,kw) OR 'superovulation'/exp OR superovulation:ti,ab,kw OR 'super ovulation':ti,ab,kw OR hyperovulation:ti,ab,kw OR 'hyper ovulation':ti,ab,kw OR 'infertility therapy'/exp OR (('assisted reproduct' NEAR/3 (techn* OR therap* OR treatment)):ti,ab,kw) OR (((fertilit OR infertilit) NEAR/3 (therap OR treatment)):ti,ab,kw) OR (((oocyte OR egg) NEAR/3 (preparat OR process* OR vitrificat* OR retriev*)):ti,ab,kw)	207228
#2	'ovary hyperstimulation'/exp/mj OR (((hyperstimulation* OR 'hyper stimulation') NEAR/3 syndrome):ti,ab,kw) OR ohss:ti,ab,kw	7815
#3	'area under the curve'/exp OR 'brier score'/exp OR 'computer prediction'/exp OR 'c statistic'/exp OR 'c statistics'/exp OR 'integrated discrimination improvement'/exp OR 'net reclassification improvement'/exp OR 'net reclassification index'/exp OR 'prediction'/exp OR 'predictive model'/exp OR 'predictive modeling'/exp OR 'predictive validity'/exp OR 'predictive value'/exp OR 'regression analysis'/exp OR 'statistical model'/exp OR 'area under the curve':ti,ab,kw OR 'brier score':ti,ab,kw OR 'c statistic' OR 'computer prediction':ti,ab,kw OR 'decision curve anal':ti,ab,kw OR (('net reclassification' NEAR/2 (improvement OR index)):ti,ab,kw) OR (((predict OR statistical) NEAR/3 (model OR validity OR value)):ti,ab,kw) OR 'proportional hazards model':ti,ab,kw OR 'r square':ti,ab,kw OR regression:ti,ab,kw OR predict:ti OR multivariate:ti,ab,kw OR multivariab:ti,ab,kw OR 'risk'/exp OR 'high risk women':ti,ab,kw OR 'risk assess':ti,ab,kw OR ((risk NEAR/3 (analys OR evaluat* OR factor*)):ti,ab,kw)	5872391
#4	#1 AND #2 AND #3	2306
#5	#4 NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp)	1384
#6	#5 AND [2000-2023]/py	1224
#7	'meta analysis'/exp OR 'meta analysis (topic)'/exp OR metaanaly:ti,ab OR 'meta analy':ti,ab OR metanaly:ti,ab OR 'systematic review'/de OR 'cochrane database of systematic reviews'/jt OR prisma:ti,ab OR prospero:ti,ab OR (((systemati OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview)):ti,ab) OR ((systemic NEAR/1 review):ti,ab) OR (((systemati OR literature OR database* OR 'data base') NEAR/10 search):ti,ab) OR (((structured OR comprehensive* OR systemic) NEAR/3 search):ti,ab) OR (((literature NEAR/3 review):ti,ab) AND (search:ti,ab OR database:ti,ab OR 'data base':ti,ab)) OR (('data extraction':ti,ab OR 'data source':ti,ab) AND 'study selection':ti,ab) OR ('search strategy':ti,ab AND 'selection criteria':ti,ab) OR ('data source':ti,ab AND 'data synthesis':ti,ab) OR medline:ab OR pubmed:ab OR embase:ab OR cochrane:ab OR (((critical OR rapid) NEAR/2 (review* OR overview* OR synthes)):ti) OR ((((critical OR rapid) NEAR/3 (review OR overview* OR synthes)):ab) AND (search:ab OR database:ab OR 'data base':ab)) OR metasynthes:ti,ab OR 'meta synthes':ti,ab	968478
#8	'major clinical study'/de OR 'clinical study'/de OR 'case control study'/de OR 'family study'/de OR 'longitudinal study'/de OR 'retrospective study'/de OR 'prospective study'/de OR 'comparative study'/de OR 'cohort analysis'/de OR ((cohort NEAR/1 (study OR studies)):ab,ti) OR (('case control' NEAR/1 (study OR studies)):ab,ti) OR (('follow up' NEAR/1 (study OR studies)):ab,ti) OR (observational NEAR/1 (study OR studies)) OR ((epidemiologic NEAR/1 (study OR studies)):ab,ti) OR (('cross sectional' NEAR/1 (study OR studies)):ab,ti)	7873980
#9	'case control study'/de OR 'comparative study'/exp OR 'control group'/de OR 'controlled study'/de OR 'controlled clinical trial'/de OR 'crossover procedure'/de OR 'double blind procedure'/de OR 'phase 2 clinical trial'/de OR 'phase 3 clinical trial'/de OR 'phase 4 clinical trial'/de OR 'pretest posttest design'/de OR 'pretest posttest control group design'/de OR 'quasi experimental study'/de OR 'single blind procedure'/de OR 'triple blind procedure'/de OR (((control OR controlled) NEAR/6 trial):ti,ab,kw) OR (((control OR controlled) NEAR/6 (study OR studies)):ti,ab,kw) OR (((control OR controlled) NEAR/1 active):ti,ab,kw) OR 'open label':ti,ab,kw OR (((double OR two OR three OR multi OR trial) NEAR/1 (arm OR arms)):ti,ab,kw) OR ((allocat NEAR/10 (arm OR arms)):ti,ab,kw) OR placebo:ti,ab,kw OR 'sham-control':ti,ab,kw OR (((single OR double OR triple OR assessor) NEAR/1 (blind* OR masked)):ti,ab,kw) OR nonrandom:ti,ab,kw OR 'non-random':ti,ab,kw OR 'quasi-experiment':ti,ab,kw OR crossover:ti,ab,kw OR 'cross over':ti,ab,kw OR 'parallel group':ti,ab,kw OR 'factorial trial':ti,ab,kw OR ((phase NEAR/5 (study OR trial)):ti,ab,kw) OR ((case* NEAR/6 (matched OR control)):ti,ab,kw) OR ((match NEAR/6 (pair OR pairs OR cohort* OR control* OR group* OR healthy OR age OR sex OR gender OR patient* OR subject* OR participant)):ti,ab,kw) OR ((propensity NEAR/6 (scor OR match)):ti,ab,kw) OR versus:ti OR vs:ti OR compar:ti OR ((compar* NEAR/1 study):ti,ab,kw) OR (('major clinical study'/de OR 'clinical study'/de OR 'cohort analysis'/de OR 'observational study'/de OR 'cross-sectional study'/de OR 'multicenter study'/de OR 'correlational study'/de OR 'follow up'/de OR cohort:ti,ab,kw OR 'follow up':ti,ab,kw OR followup:ti,ab,kw OR longitudinal:ti,ab,kw OR prospective:ti,ab,kw OR retrospective:ti,ab,kw OR observational:ti,ab,kw OR 'cross sectional':ti,ab,kw OR cross?ectional:ti,ab,kw OR multicent:ti,ab,kw OR 'multi-cent':ti,ab,kw OR consecutive:ti,ab,kw) AND (group:ti,ab,kw OR groups:ti,ab,kw OR subgroup:ti,ab,kw OR versus:ti,ab,kw OR vs:ti,ab,kw OR compar:ti,ab,kw OR 'odds ratio':ab OR 'relative odds':ab OR 'risk ratio':ab OR 'relative risk*':ab OR 'rate ratio':ab OR aor:ab OR arr:ab OR rrr:ab OR ((('or' OR 'rr') NEAR/6 ci):ab)))	14483663
#10	#6 AND #7 = SR	156
#11	#6 AND (#8 OR #9) NOT #10 = observationeel	742
#12	#6 NOT (#10 OR #11) = overig	326

Ovid/Medline

#	Searches	Results
1	exp Fertilization in Vitro/ or ((in vitro or extracorporeal) adj3 (fertilisation or fertilization)).ti,ab,kf. or ivf.ti,ab,kf. or exp sperm injections, intracytoplasmic/ or intracytoplasmic sperm injection.ti,ab,kf. or intra cytoplasmic sperm injection.ti,ab,kf. or icsi.ti,ab,kf. or exp Ovulation Induction/ or ((ovar* or ovulation) adj3 (stimulation or hyperstimulation or induc)).ti,ab,kf. or exp superovulation/ or superovulation.ti,ab,kf. or super ovulation.ti,ab,kf. or hyperovulation.ti,ab,kf. or hyper ovulation.ti,ab,kf. or (assisted reproduct adj3 (techn* or therap* or treatment)).ti,ab,kf. or ((fertilit or infertilit) adj3 (therap or treatment)).ti,ab,kf. or ((oocyte or egg) adj3 (preparat or process* or vitrificat* or retriev*)).ti,ab,kf.	101437
2	exp Ovarian Hyperstimulation Syndrome/ or ((hyperstimulation* or 'hyper stimulation') adj3 syndrome).ti,ab,kf. or ohss.ti,ab,kf.	4286
3	Area Under Curve/ or exp Forecasting/ or "Predictive Value of Tests"/ or exp Multivariate Analysis/ or exp Regression Analysis/ or exp Models, Statistical/ or area under the curve.ti,ab,kf. or brier score.ti,ab,kf. or c statistic.ti,ab,kf. or computer prediction.ti,ab,kf. or decision curve anal.ti,ab,kf. or (net reclassification adj2 (improvement or index)).ti,ab,kf. or ((predict or statistical) adj3 (model or validity or value)).ti,ab,kf. or proportional hazards model.ti,ab,kf. or r square.ti,ab,kf. or regression.ti,ab,kf. or predict.ti. or multivaria.ti,ab,kf. or exp Probability/ or 'high risk women'.ti,ab,kf. or 'risk assess'.ti,ab,kf. or (risk adj3 (analys or evaluat* or factor*)).ti,ab,kf.	3812126
4	1 and 2 and 3	879
5	4 not (comment/ or editorial/ or letter/) not ((exp animals/ or exp models, animal/) not humans/)	841
6	limit 5 to yr="2000 -Current"	707
7	meta-analysis/ or meta-analysis as topic/ or (metaanaly* or meta-analy* or metanaly).ti,ab,kf. or systematic review/ or cochrane.jw. or (prisma or prospero).ti,ab,kf. or ((systemati or scoping or umbrella or "structured literature") adj3 (review* or overview)).ti,ab,kf. or (systemic adj1 review).ti,ab,kf. or ((systemati or literature or database* or data-base) adj10 search).ti,ab,kf. or ((structured or comprehensive* or systemic) adj3 search).ti,ab,kf. or ((literature adj3 review) and (search or database* or data-base)).ti,ab,kf. or (("data extraction" or "data source") and "study selection").ti,ab,kf. or ("search strategy" and "selection criteria").ti,ab,kf. or ("data source" and "data synthesis").ti,ab,kf. or (medline or pubmed or embase or cochrane).ab. or ((critical or rapid) adj2 (review or overview* or synthes)).ti. or (((critical or rapid) adj3 (review or overview* or synthes)) and (search or database* or data-base)).ab. or (metasynthes or meta-synthes*).ti,ab,kf.	699066
8	Epidemiologic studies/ or case control studies/ or exp cohort studies/ or Controlled Before-After Studies/ or Case control.tw. or cohort.tw. or Cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective.tw. or prospective.tw. or consecutive*.tw. or Cross sectional.tw. or Cross-sectional studies/ or historically controlled study/ or interrupted time series analysis/ [Onder exp cohort studies vallen ook longitudinale, prospectieve en retrospectieve studies]	4552341
9	Case-control Studies/ or clinical trial, phase ii/ or clinical trial, phase iii/ or clinical trial, phase iv/ or comparative study/ or control groups/ or controlled before-after studies/ or controlled clinical trial/ or double-blind method/ or historically controlled study/ or matched-pair analysis/ or single-blind method/ or (((control or controlled) adj6 (study or studies or trial)) or (compar* adj (study or studies)) or ((control or controlled) adj1 active) or "open label" or ((double or two or three or multi or trial) adj (arm or arms)) or (allocat adj10 (arm or arms)) or placebo* or "sham-control" or ((single or double or triple or assessor) adj1 (blind or masked)) or nonrandom* or "non-random" or "quasi-experiment" or "parallel group" or "factorial trial" or "pretest posttest" or (phase adj5 (study or trial)) or (case adj6 (matched or control)) or (match adj6 (pair or pairs or cohort* or control* or group* or healthy or age or sex or gender or patient* or subject* or participant)) or (propensity adj6 (scor or match))).ti,ab,kf. or (confounding adj6 adjust).ti,ab. or (versus or vs or compar).ti. or ((exp cohort studies/ or epidemiologic studies/ or multicenter study/ or observational study/ or seroepidemiologic studies/ or (cohort or 'follow up' or followup or longitudinal* or prospective* or retrospective* or observational* or multicent* or 'multi-cent' or consecutive).ti,ab,kf.) and ((group or groups or subgroup* or versus or vs or compar).ti,ab,kf. or ('odds ratio' or 'relative odds' or 'risk ratio' or 'relative risk' or aor or arr or rrr).ab. or (("OR" or "RR") adj6 CI).ab.))	5530138
10	6 and 7 = SR	69
11	(6 and (8 or 9)) not 10 = observationeel	403
12	6 not (10 or 11) = overig	235

Richtlijnendatabase

Ovarieel Hyperstimulatiesyndroom