Directive clinique No 315 : Prévention du syndrome d'hyperstimulation ovarienne.

DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Acute Kidney Injury Due to Ovarian Hyperstimulation Syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a complication of assisted reproductive treatments such as in vitro fertilization (IVF). The pathophysiology of severe OHSS includes a humorally mediated capillary leak syndrome that is predominantly centered on the intra-abdominal space. Severe OHSS is frequently complicated by acute kidney injury (AKI), which can be due to any of a variety of mechanisms, each requiring a different management strategy. Mechanisms of AKI in severe OHSS include intravascular volume depletion, kidney edema due to capillary leak, intra-abdominal hypertension or compartment syndrome, and obstructive uropathy due to ovarian enlargement. We present a teaching case of severe OHSS complicated by AKI in a woman with underlying stage 4 chronic kidney disease. She had been undergoing IVF with plans to subsequently use a gestational carrier (surrogate) for pregnancy. We use this case to review the presentation and pathophysiology of OHSS complicated by AKI. In addition, we review the management of AKI in OHSS, in particular, the role of paracentesis and/or culdocentesis to manage tense ascites. Last, we highlight that similar cases may occur more frequently in the future given that IVF with subsequent use of a gestational carrier is increasingly being used for patients with comorbid conditions that can be exacerbated by pregnancy, such as advanced chronic kidney disease.

No-268-The Diagnosis and Management of Ovarian Hyperstimulation Syndrome.

OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. OUTCOMES: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. EVIDENCE: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words "ovarian hyperstimulation syndrome" and "gonadotropins," and guidelines created by other professional societies were reviewed. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report.

No. 350-Hirsutism: Evaluation and Treatment.

OBJECTIVES: To review the etiology, evaluation, and treatment of hirsutism. EVALUATION: A thorough history and physical examination plus selected laboratory evaluations will confirm the diagnosis and direct treatment. TREATMENT: Pharmacologic interventions can suppress ovarian or adrenal androgen production and block androgen receptors in the hair follicle. Hair removal methods and lifestyle modifications may improve or hasten the therapeutic response. OUTCOMES: At least 6 to 9 months of therapy are required to produce improvement in hirsutism. EVIDENCE: The quality of evidence reported in this guideline has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. RECOMMENDATIONS: Hirsutism can be slowly but dramatically improved with a 3-pronged approach to treatment: mechanical hair removal, suppression of androgen production, and androgen receptor blockade. Lifestyle changes, including weight loss and exercise, will lower serum androgen levels and improve self-esteem in patients with polycystic ovary syndrome. The patient should be educated regarding the associated health problems or long-term medical consequences of hyperandrogenism, particularly in the context of polycystic ovary syndrome, including obesity, irregular menses, anovulation, infertility, pregnancy-induced hypertension, diabetes, hyperlipidemia, hypertension, and heart disease. SUMMARY STATEMENTS: RECOMMENDATIONS.

The prevention of ovarian hyperstimulation syndrome.

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). 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. There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III) 6. Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2) 7. Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2) 8. Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) 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 prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C) 4. Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B) 5. A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C) 6. Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E) 7. Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C) 8. Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A) 9. Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B).

Objectif : Passer en revue les aspects cliniques du syndrome d'hyperstimulation ovarienne et fournir des recommandations quant à sa prévention. Options : La mise en œuvre de mesures de prévention, la constatation précoce de la présence de ce syndrome et l'offre sans délai et systématique de soins de soutien nous aideront à éviter l'obtention de piètres issues. Issues : Établir des lignes directrices permettant d'orienter la prévention du syndrome d'hyperstimulation ovarienne, la constatation précoce de la présence du syndrome lorsque ce dernier se manifeste et l'offre de mesures de soutien appropriées dans le bon contexte. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans Medline, Embase et The Cochrane Library entre 2011 et 2013 au moyen d'un vocabulaire contrôlé (« ovarian hyperstimulation syndrome ¼, « agonist IVF ¼, « antagonist IVF ¼, « metformin ¼, « HCG ¼, « gonadotropin ¼, « coasting ¼, « freeze all ¼, « agonist trigger ¼, « progesterone ¼) et de mots clés (« ovarian hyperstimulation syndrome ¼, « ovarian stimulation ¼, « gonadotropin ¼, « human chorionic gonadotropin ¼, « prevention ¼) appropriés. Les résultats ont été restreints aux analyses systématiques, aux études observationnelles et aux essais comparatifs randomisés / essais cliniques comparatifs publiés en anglais. Aucune restriction n'a été imposée en matière de date. Les recherches ont été mises à jour de façon régulière et ont été intégrées à la directive clinique jusqu'en février 2013. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Déclarations sommaires 1. La formulation particulière d'hormone folliculostimulante qui est utilisée aux fins de la stimulation ovarienne n'affecte pas l'incidence du syndrome d'hyperstimulation ovarienne. (I) 2. La pratique du « coasting ¼ pourrait atténuer l'incidence du syndrome d'hyperstimulation ovarienne grave. (III) 3. Le maintien de la pratique du « coasting ¼ pendant plus de trois jours entraîne la baisse des taux de grossesse de la fécondation in vitro. (II-2) 4. L'utilisation d'hormone lutéinisante ou de gonadotrophine chorionique humaine aux fins de la maturation finale des ovocytes n'influence pas l'incidence du syndrome d'hyperstimulation ovarienne. (I) 5. Aucune donnée probante publiée n'indique clairement que le fait d'abaisser la dose de gonadotrophine chorionique humaine entraîne une atténuation du taux de syndrome d'hyperstimulation ovarienne. (III) 6. Le cabergoline, administrée à partir du jour du déclenchement au moyen de gonadotrophine chorionique humaine, atténue l'incidence du syndrome d'hyperstimulation ovarienne chez les patientes exposées à des risques élevés et ne semble pas entraîner une baisse des taux de fécondation in vitro. (II-2) 7. Le fait d'éviter la grossesse en procédant à la congélation de tous les embryons permet de prévenir la manifestation d'un syndrome d'hyperstimulation ovarienne grave et prolongé chez les patientes exposées à des risques élevés. (II-2) 8. Lorsque les embryons sont congelés par vitrification aux fins d'un transfert à une date ultérieure, l'utilisation d'agonistes de la gonadolibérine (dans le cadre de protocoles faisant appel à des antagonistes de la gonadolibérine) pour la maturation finale des ovocytes n'affecte pas les taux de grossesse. (II-2) Recommandations 1. L'ajout d'un traitement à la metformine devrait être envisagé chez les patientes présentant le syndrome des ovaires polykystiques qui ont recours à la fécondation in vitro, puisqu'il pourrait mener à une baisse de l'incidence du syndrome d'hyperstimulation ovarienne. (I-A) 2. La posologie de gonadotrophines devrait être rigoureusement personnalisée, en tenant compte de l'âge de la patiente, de sa masse corporelle, de sa numération des follicules antraux et de sa réaction précédente aux gonadotrophines. (II-3B) 3. L'annulation du cycle avant l'administration de gonadotrophine chorionique humaine constitue une stratégie permettant de prévenir efficacement le syndrome d'hyperstimulation ovarienne; toutefois, le fardeau affectif et financier qu'une telle pratique impose aux patientes devrait être pris en considération au préalable. (III-C) 4. L'utilisation de protocoles de stimulation au moyen d'un antagoniste de la gonadolibérine est recommandée chez les patientes exposées à des risques élevés de syndrome d'hyperstimulation ovarienne. Chez les patientes qui font l'objet de protocoles aux antagonistes de la gonadolibérine et qui réagissent de façon très robuste à la stimulation ovarienne, le risque de syndrome d'hyperstimulation ovarienne grave peut être atténué en utilisant un agoniste de la gonadolibérine à titre de substitut à la gonatrophine chorionique humaine pour le déclenchement de la maturation finale des ovocytes. (I-B) 5. Pour ce qui est des donatrices d'ovocytes et dans le cadre des cycles de préservation de la fertilité, la mise en œuvre d'un protocole qui fait appel à un antagoniste de la gonadolibérine (et à un agoniste de la gonadolibérine pour le déclenchement de la maturation finale des ovocytes) est recommandée. (III-C) 6. L'utilisation d'albumine ou d'autres succédanés du plasma au moment de la récupération d'ovules n'est pas recommandée aux fins de la prévention du syndrome d'hyperstimulation ovarienne. (I-E) 7. Le transfert sélectif d'un seul embryon est recommandé aux patientes qui sont exposées à un risque élevé de syndrome d'hyperstimulation ovarienne. (III-C) 8. Pour assurer le soutien de la phase lutéale, l'utilisation de progestérone devrait être préférée à celle de gonadotrophine chorionique humaine. (I-A) 9. La tenue d'une culdocentèse en clinique externe devrait être envisagée pour la prévention de l'évolution de la maladie, en présence d'un syndrome d'hyperstimulation ovarienne grave. (II-2B).

The diagnosis and management of ovarian hyperstimulation syndrome.

OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. OUTCOMES: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. EVIDENCE: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words "ovarian hyperstimulation syndrome" and "gonadotropins," and guidelines created by other professional societies were reviewed. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). RECOMMENDATIONS: 1. Once the diagnosis of ovarian hyperstimulation syndrome is made, disease severity should be classified as mild, moderate, severe, or critical. (III-B) 2. The physician prescribing gonadotropins should inform each woman of her personal risk for ovarian hyperstimulation syndrome. (III-A) 3. In areas where patients do not have ready access to physicians familiar with the diagnosis and management of ovarian hyperstimulation syndrome, the physician prescribing gonadotropins should ensure that women are made aware that they should contact a physician or a member of the team within the hospital unit who has relevant experience, should the need arise. (III-B) 4. Outpatient management is recommended for women with mild and moderate ovarian hyperstimulation syndrome. If outpatient management for more severe ovarian hyperstimulation syndrome is to be undertaken, the physician should ensure that the woman is capable of adhering to clinical instructions and that there is a system in place to assess her status every 1 to 2 days. (III-A) 5. Paracentesis should be performed in admitted patients with tense ascites to alleviate their discomfort. (II-2B) 6. Outpatient culdocentesis should be considered for the prevention of disease progression in moderate or severe ovarian hyperstimulation syndrome. (II-2B) 7. Women with severe and critical ovarian hyperstimulation syndrome should be admitted to hospital for intravenous hydration and observation. (III-A) 8. Intravenous hydration should be initiated with a crystalloid solution to prevent hemoconcentration and provide adequate end-organ perfusion. If end-organ perfusion is not maintained with a crystalloid solution, an alternate colloid solution should be administered. (II-2B) 9. Pain relief in admitted patients should be managed with acetaminophen and/or opioid analgesics. (III-B) Non-steroidal anti-inflammatory drugs with antiplatelet properties should not be used. (III-B) 10. Women with severe ovarian hyperstimulation syndrome should be considered for treatment with prophylactic doses of anticoagulants. (II-2B) 11. Critical ovarian hyperstimulation syndrome should be managed by a multidisciplinary team, according to the end organ affected. (III-C).

Guidelines for the number of embryos to transfer following in vitro fertilization.

OBJECTIVE: To review the effect of the number of embryos transferred on the outcome of in vitro fertilization (IVF), to provide guidelines on the number of embryos to transfer in IVF-embryo transfer (ET) in order to optimize healthy live births and minimize multiple pregnancies. OPTIONS: Rates of live birth, clinical pregnancy, and multiple pregnancy or birth by number of embryos transferred are compared. OUTCOMES: Clinical pregnancy, multiple pregnancy, and live birth rates. EVIDENCE: The Cochrane Library and MEDLINE were searched for English language articles from 1990 to April 2006. Search terms included embryo transfer (ET), assisted reproduction, in vitro fertilization (IVF), ntracytoplasmic sperm injection (ICSI), multiple pregnancy, and multiple gestation. Additional references were identified through hand searches of bibliographies of identified articles. VALUES: Available evidence was reviewed by the Reproductive Endocrinology and Infertility Committee and the Maternal-Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada and the Board of the Canadian Fertility and Andrology Society, and was qualified using the Evaluation of Evidence Guidelines developed by the Canadian Task Force on the Periodic Health Exam. BENEFITS, HARMS, AND COSTS: This guideline is intended to minimize the occurrence of multifetal gestation, particularly high-order multiples (HOM), while maintaining acceptable overall pregnancy and live birth rates following IVF-ET.

Pesticide assessment: Protecting public health on the home turf.

Pesticide regulation is examined in the context of Health Canada's Pest Management Regulatory Agency's assessment of the chlorophenoxy herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) for turf. 2,4-D is the most common herbicide used to kill weeds in grass.The medical literature does not uniformly indicate harms from herbicides. However, the balance of epidemiological research suggests that 2,4-D can be persuasively linked to cancers, neurological impairment and reproductive problems. These may arise from 2,4-D itself, from breakdown products or dioxin contamination, or from a combination of chemicals.Regulators rely largely on toxicology, but experiments may not replicate exposures from 2,4-D application to lawns because environmental breakdown products (eg, 2,4-dichlorophenol) may not accumulate and selected herbicides are possibly less contaminated. Dioxins are bioaccumulative chemicals that may cause cancer, harm neurological development, impair reproduction, disrupt the endocrine system and alter immune function. No dioxin analyses were submitted to the Pest Management Regulatory Agency, and the principal contaminants of 2,4-D are not among the 17 congeners covered in pesticide regulation. Independent assessment of all dioxins is needed, in tissues and in the environment.The 2,4-D assessment does not approach standards for ethics, rigour or transparency in medical research. Canada needs a stronger regulator for pesticides. Potentially toxic chemicals should not be registered when more benign solutions exist, risks are not clearly quantifiable or potential risks outweigh benefits. Until landscaping pesticides are curtailed nationally, local bylaws and Quebec's Pesticide Code are prudent measures to protect public health. Physicians have a role in public education regarding pesticides.

Novel treatment of a patient with secondary infertility due to retained fetal bone.

OBJECTIVE: To describe a simple and previously unreported treatment for retained fetal bone fragments as a cause of secondary infertility. SETTING: Fertility center at a Canadian teaching hospital. DESIGN: Case report. PATIENT(S): A 36-year-old woman with a 15-year history of secondary infertility. INTERVENTION(S): A second dilation and curettage (D+C) performed under abdominal ultrasound guidance was performed where the curette could be directed for the removal of echogenic endometrial foci. MAIN OUTCOME MEASURE(S): Resolution of long-term infertility. RESULT(S): Spontaneous pregnancy 4 months after ultrasound-guided D+C and subsequent term delivery. CONCLUSION(S): If an echogenic area is discovered in the endometrium, it is now standard to look at the uterine cavity by hysteroscopy. However, if the hysteroscopy is normal, we suggest that a D+C with intraoperative abdominal ultrasound assistance be done to ensure that all the abnormal tissue is removed.

Timing intrauterine insemination either 33 or 39 hours after administration of human chorionic gonadotropin yields the same pregnancy rates as after superovulation therapy.

OBJECTIVE: To compare a short and long interval between hCG administration and IUI after superovulation for the treatment of infertility. DESIGN: Prospective, randomized clinical trial. SETTING: University hospital-based fertility clinic. PATIENT(S): Patients planning superovulation and IUI for the treatment of infertility. INTERVENTION(S): Patients with >or=2 years of infertility enrolled for superovulation and IUI treatment were randomized to IUI after a short (32-34-hour) or long (38-40-hour) interval after hCG injection. Superovulation was accomplished with hMG or recombinant FSH, with dose adjustment until the maturation of two to five follicles, at which time hCG was given. Sperm was prepared with a gradient centrifugation technique, with IUI performed high up in the uterine fundus. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): Of the 348 patient cycles randomized, 270 treatment cycles were initiated. Eighty-one initiated cycles were canceled, leaving 189 completed randomized cycles from 75 patients for analysis. Pregnancy rates were not significantly different between groups. There were pregnancies in 20 of the 96 short hCG-IUI interval cycles (21%) and in 14 of the 93 long hCG-IUI interval cycles (15%) (odds ratio = 0.673, 95% confidence interval 0.297-1.518). CONCLUSION(S): Pregnancy rates are the same after superovulation therapy whether IUI is done after a short or a long interval after hCG injection.

SOGC clinical practice guidelines. Hirsutism: evaluation and treatment.

OBJECTIVES: To review the etiology, evaluation, and treatment of hirsutism. EVALUATION: A thorough history and physical examination plus selected laboratory evaluations will confirm the diagnosis and direct treatment. TREATMENT: Pharmacologic interventions can suppress ovarian or adrenal androgen production and block androgen receptors in the hair follicle. Hair removal methods and lifestyle modifications may improve or hasten the therapeutic response. OUTCOMES: At least six to nine months of therapy are required to produce improvement in hirsutism. EVIDENCE: The quality of evidence reported in this guideline has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. RECOMMENDATIONS: Hirsutism can be slowly but dramatically improved with a three-pronged approach to treatment: mechanical hair removal, suppression of androgen production, and androgen receptor blockade. Lifestyle changes including weight loss and exercise will lower serum androgen levels and improve self-esteem. The patient should be educated regarding associated health problems or long-term medical consequences of hyperandrogenism, including obesity, irregular menses, anovulation, infertility, pregnancy-induced hypertension, diabetes, hyperlipidemia, hypertension, and heart disease.

The diagnosis and management of ovarian hyperstimulation syndrome: No. 268, November 2011.

OBJECTIVE: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. OUTCOMES: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. EVIDENCE: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words "ovarian hyperstimulation syndrome" and "gonadotropins," and guidelines created by other professional societies were reviewed. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1).

An investigation of the visual disturbances experienced by patients on clomiphene citrate.

OBJECTIVE: To evaluate the impact of clomiphene citrate on vision. DESIGN: Observational study. SETTING: Patients were referred to the University of Ottawa Eye Institute ophthalmology clinic from the Department of Obstetrics and Gynaecology of the Ottawa Hospital-General Campus. PATIENT(S): Eight adult females taking clomiphene citrate and experiencing visual disturbances. INTERVENTION(S): Patients received a comprehensive visual evaluation twice: once during a washout period, and once during an active clomiphene citrate treatment. MAIN OUTCOME MEASURE(S): Ophthalmologic examination, color vision, visual acuity, contrast sensitivity, visual fields using standard automated perimetry, and foveal flicker sensitivity at high (32 Hz) and low (8 Hz) temporal frequencies. RESULT(S): We found no differences between the washout and clomiphene citrate conditions for color vision, visual acuity, contrast sensitivity, and visual fields. The only statistically significant difference was found for foveal flicker sensitivity at 32 Hz in the right eye, with a similar trend in the left eye and at 8 Hz in both eyes. CONCLUSION(S): The effect of clomiphene citrate on vision was minimal, and the visual disturbances were reversible in all patients. A bilateral reduction in flicker sensitivity was the only observed visual disturbance. Women who experience visual symptoms associated with clomiphene citrate should be monitored, but therapy can usually be maintained.