The Prevention of Ovarian Hyperstimulation Syndrome

doi:10.1016/S1701-2163(15)30417-5

Journal of Obstetrics and Gynaecology Canada

Volume 36, Issue 11, November 2014, Pages 1024-1033

https://doi.org/10.1016/S1701-2163(15)30417-5 Get rights and content

Abstract

Objective

To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its prevention.

Options

Preventative measures, early recognition, and prompt systematic supportive care will help avoid poor outcomes.

Outcomes

Establish guidelines to assist in the prevention of ovarian hyperstimulation syndrome, early recognition of the condition when it occurs, and provision of appropriate supportive measures in the correct setting.

Evidence

Published literature was retrieved through searches of Medline, Embase, and the Cochrane Library from 2011 to 2013 using appropriate controlled vocabulary ([OHSS] ovarian hyperstimulation syndrome and: agonist IVF, antagonist IVF, metformin, HCG, gonadotropin, coasting, freeze all, agonist trigger, progesterone) and key words (ovarian hyperstimulation syndrome, ovarian stimulation, gonadotropin, human chorionic gonadotropin, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to February 2013.

Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Values

The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

Section snippets

Summary Statements

1.
The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I)
2.
Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III)
3.
Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2)
4.
The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I)
5.

Recommendations

1.
The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)
2.
Gonadotropin dosing should be carefully individualized, taking into account the patient’s age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B)
3.
Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the

INTRODUCTION

OHSS is a iatrogenic complication of exogenous gonadotropin therapy used to mature multiple follicles for assisted reproductive treatments. The syndrome is only rarely observed with clomiphene citrate treatment but has been reported even after spontaneous ovulation.¹ Published guidelines already exist on the management of patients suffering from severe OHSS.² The goal of this guideline is to provide a practical, evidence-based framework for the prevention of OHSS.

After gonadotropin stimulation

PREVENTION

Physicians providing ART treatment must balance the competing interests of trying to sufficiently stimulate the ovary to optimize the chance of achieving a pregnancy and minimizing the risk of severe OHSS. To achieve both of these goals both primary and secondary preventative measures have been shown to be useful.¹

Primary prevention involves identifying risk factors for OHSS and choosing an appropriate ovarian stimulation regimen. Secondary prevention involves recognizing patients who are

PROTOCOLS

Assisted reproductive technologies, especially IVF protocols, generally use GnRH agonists or antagonists to prevent an endogenous LH surge from occurring before follicular maturation. A Cochrane review of 29 RCTs showed a significantly lower incidence of OHSS in GnRH antagonist cycles than in GnRH agonist cycles (OR 0.43; 95% CI 0.33 to 0.57). Differences in rates of pregnancy or live births were not observed between the two protocols.⁴⁶

One important benefit of using GnRH antagonist protocols

SUMMARY

Risk-factors and response to ovarian stimulation are limited in their ability to assist in the prediction of OHSS disease occurrence. This becomes evident as some OHSS cases occur in patients not thought to be at significant risk, while the majority of high-risk cases do not result in OHSS.¹ Experience with controlled ovarian stimulation and knowledge of OHSS pathophysiology, risk factors, and clinical presentation remains essential for the prevention of severe OHSS.

In spite of limited

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This study aimed to assess the patient experiences and expectations related to self-injection during in vitro fertilization (IVF) treatment, and determine the recommendations of women for improving the quality of self-injection process. The data were obtained from 18 women who were in fertility treatment process at an IVF clinic between March 2020–March 2022 through in-depth and semi-structured interviews. The results were categorized into the following six themes: self-injection preparedness journey, I am afraid I cannot do it, Yes, I can do it, What if I'm not at home?, What If I do something wrong?, Do me a favor! As can be understood from the themes, women experienced fear, concern, and anxiety about self-injection. During this process, it was seen health care professionals were facilitating factors. It is thought that it is very valuable that women's suggestions such as printed material, online patient portal, alternative-colored brochures on the internet are included in the guides to be created by health professionals to facilitate self-injection practice and facilitate understanding.
Ovarian hyperstimulation syndrome
2022, Management of Infertility: A Practical Approach
Ovarian hyperstimulation syndrome (OHSS) is generally considered a potentially life-threating iatrogenic complication of the early luteal phase and/or early pregnancy caused by an excessive response to ovarian stimulation. It is characterized by cystic enlargement of the ovaries, abdominal distention and pain, and fluid shift from the intravascular space to the third space, which may eventually result in ascites, pericardial and pleural effusions, and in generalized edema. OHSS may be asymptomatic, but in some cases, it may lead to hypovolemia, hemoconcentration, electrolyte imbalances, and coagulation disorders. Moderate to severe OHSS occurs in approximately 1%–5% of in vitro fertilization cycles with an incidence of up to 20% in high-risk women. This chapter will discuss the definition, the epidemiology, the pathophysiology, the risk factors, the clinical presentation and evaluation, and the prevention and treatment strategies for OHSS using, wherever possible, evidence-based data.
Risk factors for the development of endometrial fluid in women undergoing IVF: A retrospective cohort study<sup>✰</sup>
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Main outcome measures were possible risk factors for EF, comprising PCOS, OHSS, the presence of myomas, severe endometriosis, and previous uterine surgery, including cesarean section. All the patients’ files were reviewed for the presence and description of fibroids (International Federation of Gynecology and Obstetrics (FIGO) classification) [15], diagnosis of severe endometriosis (revised American Fertility Society (rAFS) stage 3 or 4) [16], diagnosis of PCOS according to the Rotterdam criteria, previous pelvic or uterine surgery including cesarean section, myomectomy (all approaches: abdominal, laparoscopic or hysteroscopic myomectomy), previous endometrial surgery (i.e. operative hysteroscopy for polypectomy or adhesions treatment) and OHSS during the IVF cycle, according to the Society of Obstetricians and Gynaecologists of Canada (SOGC) criteria [17]. We therefore focused on ovarian response, diagnosis of PCOS and endometriosis, as suggested by other authors [2], but we also added uterine fibroids as well as previous uterine surgery as potential risk factors, based on our clinical observations.
Presence of endometrial fluid (EF) is a poorly understood pathology and remains a challenge for clinicians, as very little data exists to explain its consequences and treatment. Our objective was to investigate risk factors for EF during IVF.
This retrospective cohort study included all women with a freeze all embryos cycle (FAE) for EF between 2010 and 2016 at a university-affiliated private IVF center. Controls (2:1) were randomly selected out of the database of our fresh autologous IVF cycles during the same period. Main outcome measures were possible risk factors for EF, comprising polycystic ovarian syndrome (PCOS), ovarian hyperstimulation syndrome (OHSS), previous pelvic or endometrial surgery (polypectomy or synechia removal), cesarean section, myomas and severe endometriosis. A logistic regression model was used to assess independent risk factors for EF.
Out of 9000 IVF cycles, 1204 were FAE cycles, among which we identified 86 EF cases. We then selected 171 controls. Independent risk factors for presence of EF were a history of previous myomectomy (adjusted odds ratio (aOR) 19.77, 95%CI [4.01–97.53]), severe endometriosis (aOR 5.97, 95%CI [2.09–17.05]), PCOS (aOR 5.72, 95%CI [2.66–12.33]) and previous cesarean section (aOR 5.17, 95%CI [1.84–14.49]).
Our results are not only confirming the association between PCOS, severe endometriosis, previous cesarean procedure and EF, but also reporting for the first time an association between previous myomectomy and EF.
The ART of medicine: Counselling women with liver disease about assisted reproductive technology
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Use of cabergoline and post-collection GnRH antagonist administration for prevention of ovarian hyperstimulation syndrome
2019, Reproductive BioMedicine Online
Citation Excerpt :
A number of strategies for active prevention of OHSS have been described (Guo et al., 2016; Humaidan et al., 2010; Mathur et al., 2007). In patients at risk for developing OHSS, final oocyte maturation with GnRH agonists, which induce an endogenous rise in LH concentrations, is the most efficient method to prevent OHSS (Pfeifer et al., 2016; Corbett et al., 2014; Kol and Itskovitz-Eldor, 2000; Mourad et al., 2017), although it does not eliminate the risk (Fatemi et al., 2014). The duration of this LH surge is 14 h as compared with the human chorionic gonadotrophin (HCG) used to trigger ovulation, which functions for 7 days or more, resulting in prolonged ovarian stimulation and increased OHSS rates.
Does the addition of a gonadotrophin-releasing hormone (GnRH) antagonist to cabergoline treatment during the luteal phase in fresh IVF cycles triggered with a GnRH agonist, and planned for freeze-all, reduce the rate of mild and moderate ovarian hyperstimulation syndrome (OHSS)?
Retrospective cohort study of 480 IVF patients at risk for OHSS with GnRH agonist trigger from 2011 to 2018, stratified into three groups based on treatment received: GnRH agonist trigger alone (Group 1, n = 208), GnRH agonist trigger + cabergoline (Group 2, n = 167) or GnRH agonist trigger + cabergoline + GnRH antagonist (Group 3, n = 105). Data on patient demographics, incidence, severity and symptomatology of OHSS and laboratory findings were collected.
Group 1 had more free peritoneal fluid than Group 2 (28% versus 19%, P = 0.04) or Group 3 (28% versus 5%, P = 0.001). Group 1 reported abdominal discomfort and bloating more than Group 2 (33% versus 21%, P = 0.01) or Group 3 (33% versus 18%, P = 0.006). Group 1 had more electrolyte abnormalities than Group 2, who had more than Group 3. No patients developed severe OHSS. Mild and moderate OHSS rate was higher in Group 1 (38%) than Group 2 (29%, P = 0.048) or Group 3 (18%, P = 0.006) and in Group 2 than Group 3 (P = 0.046).
Addition of cabergoline to GnRH agonist triggering in high-risk OHSS patients, and subsequent addition of GnRH antagonist for 5 days in the luteal phase, sequentially reduces the risk of mild and moderate OHSS and improves patient comfort compared with GnRH agonist trigger alone.
Triggering method in assisted reproduction alters the cumulus cell transcriptome
2019, Reproductive BioMedicine Online
Citation Excerpt :
The GnRH-ant based protocols can yield comparable pregnancy outcomes to GnRH-ag based ‘long protocols’ (Lin et al., 2014). By utilizing GnRH-ag for triggering final oocyte maturation in lieu of HCG, the LH receptor activity is shortened, and VEGF levels are lowered, thereby minimizing the risk of OHSS (Babayof et al., 2006; Corbett et al., 2014; DiLuigi et al., 2010; Humaidan, 2006; Melo et al., 2009; Moyle et al., 1975). Another potential advantage of incorporating GnRH-ag into the trigger step is the induction of an endogenous FSH surge, in addition to the endogenous LH surge, which enhances nuclear maturation of the oocyte (Griesinger et al., 2006, 2007; Shalev et al., 1994).
How does the choice of triggering final oocyte maturation affect the cumulus cell transcriptome?
Sixty patients undergoing gonadotrophin-releasing hormone antagonist (GnRH-ant) IVF cycles were recruited for this nested case–control study. Patients were stratified into three subgroups based on their ovarian reserve (high, normal and low). Triggering final oocyte maturation was accomplished by either single trigger (with human chorionic gonadotrophin [HCG] only or gonadotrophin-releasing hormone agonist [GnRH-ag] only) or dual trigger combining HCG and GnRH-ag. The choice of trigger was at the discretion of the treating physician. Within each group patients receiving a dual trigger were matched by demographic and pre-stimulation parameters with patients receiving a single trigger. The matching was performed to minimize the biological variability within each subgroup. Thirty patients were included in the final analysis. Cumulus cells were stripped away from the retrieved oocytes. Cumulus cells from three sibling oocytes were pooled, the RNA extracted and libraries prepared. Next-generation sequencing was performed on all samples.
Dual triggering supports key ovarian pathways of oocyte maturation and extracellular matrix remodelling, while attenuating vasculo-endothelial growth and providing antioxidant protection to the growing follicles.
This is the first study to delineate key transcriptomic changes under dual triggering of final oocyte maturation, across different patient populations. The findings underline the need for larger-scale studies validating transcriptomic effects of methods for triggering final oocyte maturation. Furthermore, there is a need for large-scale clinical randomized controlled studies to relate the findings of this study with clinical outcomes.

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This clinical practice guideline has been prepared by the Reproductive Endocrinology Infertility Committee and approved by Executive and Council of the Society of Obstetricians and Gynaecologists of Canada.

Disclosure statements have been received from all contributors.

: This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be reproduced in any form without prior written permission of the SOGC.

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SOGC CLINICAL PRACTICE GUIDELINEThe Prevention of Ovarian Hyperstimulation Syndrome

Abstract

Objective

Options

Outcomes

Evidence

Values

Section snippets

Summary Statements

Recommendations

INTRODUCTION

PREVENTION

PROTOCOLS

SUMMARY

J Obstet Gynaecol Can

Fertil Steril

Am J Obstet Gynecol

Fertil Steril

Fertil Steril

Am J Obstet Gynecol

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Vascul Pharmacol

Reprod Biomed Online

Fertil Steril

Fertil Steril

Fertil Steril

Fertil Steril

Reprod Biomed Online

Fertil Steril

Reprod Biomed Online

Rep Bio Med Online

Fertil Steril

Fertil Steril

Review of the evidence base of strategies to prevent ovarian hyperstimulation syndrome

Hum Fertil

Ovarian hyperstimulation syndrome: an update review

Obstet Gynecol Surv

Conservative management of ovarian hyperstimulation syndrome

J Reprod Med

An autopsy case of ovarian hyperstimulation syndrome with massive pulmonary edema and pleural effusion

Pathol Int

Epidemiology and prevention of ovarian hyperstimulation syndrome (OHSS): a review

Hum Reprod Update

Review of clinical course and treatment of ovarian hyperstimulation syndrome (OHSS)

Hum Reprod Update

Human chorionic gonadotripin-dependent expression of vascular endothelial growth factor/vascular permeability factor in human granulose cells: importance in ovarian hyperstimulation syndrome

J Clin Endocrinol Metab

SOGC CLINICAL PRACTICE GUIDELINE
The Prevention of Ovarian Hyperstimulation Syndrome