Management of severe early ovarian hyperstimulation syndrome by re-initiation of GnRH antagonist

Several approaches have been proposed for the management of OHSS that reduce, but do not completely eliminate the incidence of human chorionic gonadotrophin (HCG)-induced early severe OHSS. Three women diagnosed with polycystic ovarian syndrome underwent ovarian stimulation for IVF using a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Three days after oocyte retrieval, severe early OHSS was diagnosed by analysis of haematocrit (Ht), white blood cell (WBC) count, serum urea, and ultrasonographic assessment of ovarian size and ascitic fluid. On the same day, antagonist administration was re-initiated and continued daily for a week, while all embryos were cryopreserved. No progression of severe early OHSS was observed in any of the patients. A marked decrease of Ht, WBC count, ovarian volume and ascitic fluid was observed during 1 week of follow-up, and none of the patients required hospitalization. GnRH antagonist re-initiation might represent a new strategy for flexible management of patients with established severe early OHSS. Based on the flexibility of the approach, if severe OHSS does not occur, patients may proceed to embryo transfer, while if severe early OHSS ensues, antagonist administration combined with embryo cryopreservation appear to be associated with prevention of life-threatening OHSS, facilitation of regression of severe OHSS to a moderate form and avoidance of patient hospitalization.     

Prospective study of the clinical and laboratory parameters of patients in whom ovarian hyperstimulation syndrome developed during controlled ovarian hyperstimulation for in vitro fertilization

OBJECTIVE: To compare patient characteristics and clinical and laboratory parameters in patients in whom ovarian hyperstimulation syndrome (OHSS) develops with those in whom it does not develop. DESIGN: Prospective cohort study. SETTING: Reproductive medicine unit at a university medical center. PATIENT(S): All patients undergoing IVF (n = 428) who received controlled ovarian hyperstimulation during a 6-month period. INTERVENTION(S): Prospective data collection. MAIN OUTCOME MEASURE(S): Patient characteristics (age, body mass index, medical history, smoking habits) and clinical and laboratory data obtained during controlled ovarian hyperstimulation were evaluated in patients who had severe OHSS, any degree of OHSS, or a significant risk of OHSS and compared with the remaining populations. RESULT(S): Severe OHSS developed in 18 patients (4.2%) and mild or moderate OHSS developed in 7.3%. As a group, all the patients with OHSS were significantly younger, received lower doses of gonadotropins, had ovaries containing a higher number of total and large follicles, had a higher number of retrieved oocytes, and had a higher pregnancy rate than the patients without OHSS. The patients with severe OHSS also had an increased prevalence of allergy (56% versus 21%) and were more likely to ultimately give birth. CONCLUSION(S): The observed differences may be useful in elucidating the pathophysiology of OHSS and identifying patients who are at increased risk for OHSS.     

Neue Ansätze bei der Prävention des ovariellen Überstimulationssyndroms

Severe ovarian hyperstimulation syndrome (OHSS) is a rare and potentially life-threatening complication of ovarian stimulation for IVF. The crucial issue about OHSS is prevention, rather than treatment. One factor to preventing OHSS is recognition of risk factors. Among risk factors such as polycystic ovarian syndrome (PCOS), rapidly rising serum estradiol levels during ovarian stimulation, and previous episodes of OHSS, the number of preovulatory follicles has been shown to have the highest sensitivity and specificity to identify the patients with subsequent development of OHSS. More recently, follicle-stimulating hormone (FSH) receptor polymorphisms and anti-muellerian hormone (AMH) have been suggested to be predictive in the development of the disease, but existing data are conflicting or insufficient. As none of the available clinical algorithms will identify all patients at risk of OHSS, future IVF treatment regimen should routinely employ means that reduce the incidence of the syndrome (GnRH-antagonist protocols, mild stimulation). However, no modification to current ovarian stimulation regimen will be 100% effective in preventing severe OHSS, therefore OHSS prevention by replacing the ovulation-inducing trigger of human chorionic gonadotropin (hCG) with a bolus dose of GnRH-agonist has recently attained great interest. Further novel concepts in OHSS incidence reduction, such as coasting with antagonist, reduced dose of hCG, administration of a VEGF receptor antagonist after oocyte pick-up, and luteal phase antagonist administration will selectively be discussed in this literature review.     

Plasma levels of free vascular endothelial growth factor(165) (VEGF(165)) are not elevated during gonadotropin stimulation in in vitro fertilization (IVF) patients developing ovarian hyperstimulation syndrome (OHSS): results of a prospective cohort study with matched controls

OBJECTIVE: To evaluate whether differences in plasma vascular endothelial growth factor(165) (VEGF(165)) concentrations exist during gonadotropin stimulation in IVF patients developing severe ovarian hyperstimulation syndrome (OHSS) compared to matched controls. STUDY DESIGN: Prospective cohort study with comparison of 15 OHSS cases with 30 matched (age, follicle numbers, pregnancy) controls. Unpaired students t-test was used to evaluate differences between the OHSS and control group and correlations were calculated with Pearson's test. RESULT(S): Plasma levels of VEGF(165), at four time-points from start of gonadotropin stimulation to embryo transfer (ET), were compared and related to steroid levels and ultrasound data. There were no differences between OHSS and control patients in plasma VEGF(165) levels at any of the four time points, which were compared. The mean levels were between 53--83 pg ml(-1) and 64--83 pg ml(-1) in the OHSS and control group, respectively. Positive correlations existed between total number of follicles, number of large (>15 mm) follicles and VEGF(165) at day of oocyte aspiration and between VEGF(165) and progesterone at ET in the control group, but not in the OHSS group.CONCLUSION(S): Patients developing OHSS do not have raised plasma VEGF(165) levels during gonadotropin stimulation. The lack of positive correlation between VEGF(165) levels and follicle numbers/progesterone in the OHSS group, suggests a disruption in OHSS of the normal controlled follicular VEGF expression.     

Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide®) in controlled ovarian stimulation for assisted reproduction

A prospective, randomized study was performed to compare the efficiency of hormonal stimulation for IVF (in vitro fertilization) in either the long luteal protocol, using the LHRH agonist Buserelin, or the multiple dose LHRH antagonist protocol, using the LHRH antagonist Cetrorelix. Here we present the data on the incidence of ovarian hyperstimulation syndromes (OHSS). 85 and 188 patients were recruited for the stimulation in the LHRH agonist and in the LHRH antagonist protocol, respectively. The groups were comparable regarding anamnestic data. The incidence of WHO °II and °III OHSS was significantly lower in the Cetrorelix than in the Buserelin group (1.1% vs. 6.5%, p=0.03). Additionally 3 patients in the Cetrorelix group (1.6%) and 5 patients in the Buserelin group (5.9%) did not receive hCG because of a threatening OHSS. The follicle maturation was more homogeneous in the Cetrorelix protocol, with less small follicles on the day of hCG administration but a similar number of oocyte cumulus complexes retrieved. The pregnancy rates per cycle were not significantly different in the Cetrorelix and Buserelin protocol (22% vs. 26%). The Cetrorelix multiple dose protocol is advantageous compared to the long protocol regarding the incidence of OHSS, a potentially life threatening complication of controlled ovarian stimulation. Received: 24 March 2000 / Accepted: 7 April 2000     

多囊卵巢综合征(PCOS)患者在IVF-ET中发生严重卵巢过度刺激综合征(OHSS)的特点分析

目的:通过总结IVF-ET中多囊卵巢综合征(PCOS)患者应用控制性超促排卵(COH)后发生卵巢过度刺激综合征(OHSS)的特点,提出防止中、重度OHSS发生的有效措施。方法:将IVF/ICSI治疗时出现中、重度OHSS的患者根据有无PCOS史分成PCOS组和对照组。比较分析PCOS组和非PCOS组在COH中的雌激素水平、卵泡数、取卵数及发生中、重度OHSS的时间等临床资料;分析妊娠对OHSS的影响。结果:PCOS组的Gn用药总量及hCG注射日的血清E2水平比对照组低,其总卵泡数、中小卵泡数明显高于对照组,发生中、重度OHSS的时间早,妊娠可能加重OHSS病情发展。结论:卵泡总数、中小卵泡数可作为PCOS患者预测中、重度OHSS独立的重要指标,建议即使取卵前E2水平不高、获卵数不多也考虑行全胚冷冻,以阻止严重的OHSS发生。     

Live births after management of severe OHSS by GnRH antagonist administration in the luteal phase

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian stimulation protocols. Currently, no curative therapy exists and the main preventive option is cycle cancellation. Gonadotrophin-releasing hormone (GnRH) antagonist administration in the luteal phase was recently proposed as a new approach for the management of patients with established severe OHSS. Three polycystic ovarian syndrome patients undergoing IVF treatment developed severe OHSS, diagnosed 6 days after oocyte retrieval. On day 6, the patients underwent blastocyst transfer and received GnRH antagonist for 4 days, combined with luteal phase support using exogenous oestradiol and progesterone. Two patients had successful pregnancies that resulted in births of healthy infants, while one patient had a biochemical pregnancy. In all patients, established severe OHSS regressed to a moderate form of the syndrome, no pregnancy-induced life-threatening OHSS was observed, while a short monitoring period was required at an outpatient level, avoiding the need for patient hospitalization. This is the first report in the literature on GnRH antagonist administration in the luteal phase, combined with embryo transfer and exogenous oestradiol and progesterone supplementation. This novel treatment was effective in the regression of established severe OHSS, and resulted in the birth of healthy infants.     

The value of routine estradiol monitoring in assisted conception cycles

BACKGROUND: Traditional monitoring of an in vitro fertilization (IVF) treatment cycle includes regular estradiol levels and ultrasound scans in an attempt to reduce the risk of ovarian hyperstimulation syndrome (OHSS). The need for estradiol monitoring remains controversial. METHODS: We reviewed 538 consecutive cycles of IVF that were carried out in our unit to ascertain whether routine estradiol monitoring was of help in preventing OHSS and could be used to predict treatment outcome. Two hundred and sixty-eight patients had their ovarian response monitored with ultrasound (USS) and estradiol levels on the day of hCG administration. The following 270 had USS monitoring but only had an estradiol level checked if they were deemed to be at high risk of OHSS (> 20 follicles on USS or symptomatic). RESULTS: Pregnancy rates per treatment cycle and per embryo transfer were similar in the two groups (all p > 0.05). There were two patients in each group requiring admission to hospital for OHSS. CONCLUSIONS: Estradiol levels did not correlate with IVF outcome. In summary therefore estradiol levels are a poor predictor of treatment success and done routinely do not reduce the incidence of OHSS. It is only necessary to measure the estradiol level in those patients at risk of OHSS on USS monitoring.     

Serum vascular endothelial growth factor levels before starting gonadotropin treatment in women who have developed moderate forms of ovarian hyperstimulation syndrome.

The study aims to evaluate whether serum vascular endothelial growth factor (VEGF) levels, before treatment with gonadotropins, may be considered a predictive marker of moderate ovarian hyperstimulation syndrome (OHSS). At the University of Pisa hospital infertility unit we have retrospectively selected 10 patients who developed moderate forms of OHSS and 30 control patients who presented a normal response to ovarian stimulation among 400 women undergoing in vitro fertilization (IVF). Serum samples were collected before starting pFSH administration (150-300 IU/day). VEGF levels in serum were measured. No statistically significant difference was found between the serum VEGF levels of patients who developed moderate forms of OHSS and women without any symptoms of the syndrome. Further, serum VEGF concentrations were not significantly correlated with the age of the patients, the number of international units of FSH administered during the cycle of stimulation, the follicle and oocyte numbers counted on the day of the egg retrieval or estradiol levels detected on the same day. This study demonstrates that serum VEGF levels, before starting gonadotropin treatment, are not predictive of the subsequent development of moderate forms of ovarian hyperstimulation syndrome.     

Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders

Objective: To describe the different clinical and laboratory diagnostic methods (basal and dynamic tests) available to identify poor-, good-, and high-responder patients undergoing treatment with in vitro fertilization (IVF).

Design: Analytical review.

Setting: IVF program.

Patients: Women in different age groups undergoing IVF treatment.

Intervention(s): Assessment of clinical and laboratory parameters and correlation with outcomes.

Main Outcome Measure(s): Response to ovarian stimulation and success of the assisted reproductive technologies (ART).

Result(s): Age, basal follicle-stimulating hormone (FSH), estradiol and inhibin-B levels, and dynamic testing serve to predict individual response to ovarian stimulation for ART.

Conclusion(s): Markers of ovarian reserve (day 3 FSH, inhibin B and E₂) are particularly predictive and useful in guiding the choice of the optimal protocol for ART. However, no tests are absolutely predictive of a successful outcome. For the younger individual, and for the patient at risk of developing ovarian hyperstimulation syndrome (OHSS), assessment and identification of clinical and laboratory parameters predictive of a high response to ovarian stimulation should guide the clinician in choosing an appropriate stimulation protocol, thus attenuating the risk of OHSS.     

GnRH agonist trigger with intensive luteal phase support vs. human chorionic gonadotropin trigger in high responders: an observational study reporting pregnancy outcomes and incidence of ovarian hyperstimulation syndrome

A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had?≥18 follicles?≥11mm or serum oestradiol?>18,000pmol/l on the day of trigger. Patients had a single or double embryo transfer at cleavage or blastocyst stage. Logistic regression was used to adjust for differences between the groups. An intention-to-treat analysis of all cycles was performed. No statistically significant differences were observed in terms of positive pregnancy test, clinical pregnancy rate and live birth rate. Only one patient (0.3%) was hospitalized with severe OHSS in the GnRHa group, compared to 26 patients (13%) in the hCG group. In conclusion, GnRHa trigger is associated with similar pregnancy rates with hCG trigger and a significant reduction in hospitalization for severe OHSS after an intention to treat analysis was performed.     

卵母细胞体外成熟预防卵巢过度刺激综合征的应用

目的:探讨卵母细胞体外成熟预防卵巢过度刺激综合征(ovarian hyperstim- ulation syndrome,OHSS)的效果。方法:51例IVF长方案超排卵过程中出现OHSS早期征象时,按患者意愿分成两组,实验组于当天注射人绒毛膜促性腺激素(hCG)36h后取卵,经体外培养成熟行体外受精、胚胎移植;对照组则继续按常规用药方案及受精方案行胚胎移植。测定两组出现OHSS早期征象当日的E_2、统计FSH用药天数、用药量、受精率及临床妊娠率。结果:实验组与对照组在出现OHSS早期征象当日的血E_2水平、受精率、优质胚胎率、临床妊娠率无统计学差异;但实验组的FSH总用量、FSH用药天数、获卵数方面显著低于对照组(P<0.05)。实验组1例发生中度OHSS,对照组则发生3例重度OHSS和2例中度OHSS,重度OHSS发生率差异极显著(P<0.01)。结论:超排卵过程中,出现OHSS早期征象时改行卵母细胞体外成熟培养技术可有效地降低OHSS的发生率。     

Use of Stimulated Serum Estradiol Measurements for the Prediction of Hyperresponse to Ovarian Stimulation in in Vitro Fertilization (IVF)

PURPOSE: In ovarian stimulation an exaggerated ovarian response is often seen and is related to medical complications, such as ovarian hyperstimulation syndrome (OHSS), and increased patient discomfort. If it were possible to identify hyperresponders at an early stage of the stimulation phase, adaptation of the stimulation protocol would become feasible to minimize potential complications. Therefore, we studied the usefulness of measuring stimulated serum estradiol (E2) levels in predicting ovarian hyperresponse. METHODS: A total of 109 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. The E2 level was evaluated on day 3 and 5 of the stimulation phase. Two outcome measures were defined. The first was ovarian hyperresponse (collection of > or = 15 oocytes at retrieval and/or peak E2 > 10000 pmol/L, or cancellation due to > or = 30 follicles growing and/or peak E2 > 15000 pmol/L, or OHSS developed). The second outcome measure comprised a subgroup representing the more severe hyperresponders. named extreme-response (cancellation or OHSS developed). RESULTS: The data of 108 patients were analyzed. The predictive accuracy of E2 measured on stimulation day 3 towards ovarian hyperresponse was clearly lower than that of E2 measured on stimulation day 5 (area under the receiver operating characteristic curve (ROCAUC) 0.75 and 0.81, respectively). For extreme-response the predictive accuracy of E2 measured on stimulation day 3 or 5 was comparable (ROCAUC 0.81 and 0.82, respectively). For both outcome measures the stimulated E2 tests yielded only acceptable specificity with moderate sensitivity at higher cutoff levels. Prediction of extreme-response seemed slightly more effective due to a lower error rate. CONCLUSIONS: There is a significant predictive association between E2 levels measured on stimulation day 3 and 5 and both ovarian hyperresponse and extreme-response in IVF. However, the clinical value of stimulated E2 levels for the prediction of hyperresponse is low because of the modest sensitivity and the high false positive rate. For the prediction of extreme-response the clinical value of stimulated E2 levels is moderate.     

Risiken der ovariellen Stimulation zur IVF

This text aims at reviewing proposed and proven risks associated with ovarian stimulation for IVF. A Medline search was performed and relevant studies are selectively cited. The risk of adnexal torsion, ovarian hyperstimulation syndrome (OHSS), thrombosis and embolism, epigenetic alterations, prion transmission via urinary gonadotrophins and cancer are summarized and discussed. The incidence of adnexal torsion, OHSS and thrombosis after ovarian stimulation for IVF has been determined in large, but heterogeneous populations. For patient counseling, individual risk factors should be taken into consideration. The contention of a risk of epigenetic alterations caused by ovarian stimulation is not supported by sound clinical data. No case of prion transmission from urinary derived gonadotrophins has been observed, therefore, this risk has to be considered theoretical. A relationship between ovulation-inducing drugs and increased cancer incidence has been suggested by a number of studies, however, a causal association has not yet been demonstrated.     

GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized,prospective, controlled,assessor-blind study

The use of gonadotrophin-releasing hormone (GnRH) agonists for triggering ovulation remains controversial. The primary objective of this study was to evaluate the incidence of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist versus recombinant human chorionic gonadotrophin (HCG) as methods for triggering ovulation. A second aim was to compare the clinical outcome and embryo quality according to the two procedures. The cycle characteristics of 100 oocyte donors undergoing ovarian stimulation and IVF outcomes of their 100 oocyte recipients were analysed. Donors were prospectively randomized into two groups on the last day of ovarian stimulation: Group I received a single bolus of 0.2 mg of triptorelin and Group II received 250 μg of recombinant HCG. No differences were observed in the number of oocytes retrieved or in the proportion of metaphase II oocytes between the groups. The OHSS rate was higher in donors that received recombinant HCG (P = 0.003). Moreover, there was no significant difference between IVF parameters and outcome in the two groups. In conclusion, a GnRH agonist effectively triggers the final oocyte maturation in oocyte donors without negatively affecting implantation, pregnancy or miscarriage rates. Moreover, this regime effectively eliminates the risk of OHSS in this group of women.     

Substituting HCG with GnRH agonist to trigger final follicular maturation--a retrospective comparison of three different ovarian stimulation protocols

The study retrospectively evaluated the influence of triggering final oocyte maturation with gonadotrophin-releasing hormone (GnRH) agonist on the outcome of IVF cycles. Four hundred and sixty consecutive women admitted to the IVF unit during a 4-year period were enrolled in the study. Ovarian stimulation characteristics and clinical pregnancy rate were compared between three groups: patients at risk of developing ovarian hyperstimulation syndrome (OHSS), undergoing either the long GnRH-agonist protocol (agonist group) or the flexible multidose GnRH-antagonist protocol who received GnRH-agonist for final oocyte maturation (antagonist-agonist group); and patients not at risk of developing severe OHSS undergoing the flexible multidose GnRH-antagonist protocol who received human chorionic gonadotrophin (HCG) for final oocyte maturation (antagonist-HCG group). Implantation and clinical pregnancy rates were lowest in the antagonist-agonist group despite the fact that no difference were was observed in fertilization rates between the groups. Moreover, the high-responder antagonist-agonist group required shorter stimulation and had higher numbers of oocytes retrieved as compared with the high-responder agonist-group. No case of severe OHSS was observed in the antagonist-agonist group. The use of flexible multidose GnRH-antagonist protocol with GnRH-agonist for final oocyte maturation, in high-responder patients, eliminates the risk of OHSS but results in decreased implantation and pregnancy rates.     

卵泡刺激素刺激后血清抑制素B和雌二醇预测体外受精周期中卵巢的反应性及其相关性

目的 探讨以经重组卵泡刺激素（rFSH）刺激后体外受精（IVF）周期中不同时间血清抑制素B（INHB）、雌二醇（E2）的动态变化,预测不孕患者卵巢的反应性,为选择最佳的超促排卵方案提供理论依据。方法 采用酶联免疫吸附试验,测定57例不孕患者（年龄〈40岁）于IVF周期中的不同时问,即月经第3天、注射rFSH前、注射rFSH后1d,及注射rFSH后5d的血清INHB、E2水平,并与反映卵巢反应性的2个指标——获卵数／rFSH总量、（卵泡数／rFSH总量）的平方根进行相关性分析。根据本研究中卵泡数及获卵数、是否发生卵巢过度刺激综合征（OHSS）的情况,将57例患者分为低反应组、过度刺激组及正常反应组,比较3组注射rFSH后INHB及E2水平的变化。结果 （1）注射rFSH后1、5d,其血清INHB及E：水平均与卵巢反应性呈显著正相关（INHB：rS=0．69—0．73,E2：rS=0．60～0．73;P=0．000）。（2）低反应组、正常反应组及过度刺激组注射rFSH后5d,患者血清INHB水平分别为164．7、696．2及1263．5ng／L,E2水平分别为303．2、1709．5及4261．0pmol／L,低反应组明显低于正常反应组,正常反应组明显低于过度刺激组,3组分别比较,差异均有统计学意义（P（0．01）。结论 经rFSH刺激后,血清INHB及E2水平能较敏感地预测卵巢对rFSH刺激的反应性,且INHB比E2更敏感。INHB及E2水平降低,可预测卵巢的低反应性;反之,可预测发生OHSS。     

What is the best predictor of severe ovarian hyperstimulation syndrome in IVF? A cohort study

Purpose

The purpose of the present study is to study what is the best predictor of severe ovarian hyperstimulation syndrome (OHSS) in IVF.

Methods

This is a retrospective analysis of all consecutive IVF/intracytoplasmic injection cycles performed during a 5-year period (2009–2014) in a single university fertility centre. All fresh IVF cycles where ovarian stimulation was performed with gonadotrophins and GnRH agonists or antagonists and triggering of final oocyte maturation was induced with the administration of urinary or recombinant hCG were analyzed (2982 patients undergoing 5493 cycles). Because some patients contributed more than one cycle, the analysis of the data was performed with the use of generalized estimating equation (GEE).

Results

Severe OHSS was diagnosed in 20 cycles (0.36%, 95% CI 0.20–0.52). The number of follicles ≥10 mm on the day of triggering final oocyte maturation represents the best predictor of severe OHSS in IVF cycles. The cutoff in the number of follicles ≥10 mm with the best capacity to discriminate between women that will and will not develop severe OHSS was ≥15.

Conclusion

The presence of more than 15 follicles ≥10 mm on the day of triggering final oocyte maturation represents the best predictor of severe OHSS in IVF cycles.

     

A novel approach for patients at risk for ovarian hyperstimulation syndrome: elective transfer of a single zona-free blastocyst on day 5

In this preliminary prospective randomized study of 420 patients undergoing ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI), 17 patients (4%) developed moderate to severe ovarian hyperstimulation syndrome (OHSS). Re-evaluation for OHSS on day 4 and 6 after oocyte retrieval identified one patient with continuous risk for severe OHSS, resulting in cancellation of the transfer (1/17, 5.8%). Prospectively, two of three patients had the zona pellucida of the blastocyst removed by pronase exposure prior to transfer. Significantly more patients became pregnant when a zona-free blastocyst was transferred in comparison to transfer of a single zona-intact embryo (9/11 or 82% versus 1/5 or 20%; P < 0.01). Higher ongoing singleton pregnancy rates were obtained when the zona pellucida was removed prior to the transfer (6/11 and 1/5 respectively). This preliminary prospective randomized study indicates that by prolonging the evaluation time for patients at risk of developing OHSS for up to 6 days after the oocyte retrieval, those patients at risk for developing severe OHSS can be identified. Transferring a single zona-free day 5 embryo (blastocyst) and freezing of the supernumerary embryos offers the patient with moderate OHSS an optimal chance for a singleton pregnancy, while avoiding the serious maternal complications of ovarian hyperstimulation syndrome.     

Outcome of IVF pregnancies following severe OHSS

Because severe ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening iatrogenic complication, much effort is made to prevent it and the anticipated pregnancy naturally becomes of secondary importance. There are many publications on OHSS, but very few on pregnancy outcomes. This work is to review the effect of OHSS on pregnancy outcome along the pregnancy course. Hospitalized patients with severe OHSS are exposed to several insults that could affect pregnancy outcome in its early stages: the ovarian hyperstimulation for IVF itself, haemodynamic instability that involve haemoconcentration, hypoxia, liver and renal dysfunction, and exposure to high endogenous oestrogens, cytokines, renin, angiotensin and prostaglandins. There is a paucity of data on the relation of OHSS and pregnancy complications. The incidence of multiple pregnancies, gestational diabetes mellitus, placental abruption prematurity and low birthweight is higher in cases of pregnancy complicated by severe OHSS. Therefore, these pregnancies should be considered as high-risk pregnancies, and followed/treated as such. As prevention is the best ‘treatment’ for OHSS, this may imply the need for more patient-friendly or mild stimulation protocols.