Manejo del Síndrome de Hiperestimulación Ovárica / Management of Ovarian Hyperstimulation Syndrome

INTRODUCCIÓN: El síndrome de hiperestimulación ovárica es una respuesta exagerada del ovario a los tratamientos hormonales para estimular la formación de óvulos. OBJETIVO: Describir el caso clínico de una mujer con síndrome de hiperestimulación ovárica; revisar el abordaje, manejo, tratamiento y cómo prevenirlo. CASO CLÍNICO: Paciente femenina de 37 años, multigesta, en tratamiento con metformina por Síndrome de ovario poliquístico , que presenta infertilidad secundaria a factor tubárico, que desarrolló un cuadro moderado de síndrome de hiperestimulación ovárica como consecuencia de la aplicación de las técnicas de fertilización in vitro (Folitropina alfa humana recombinante (GONAL-F®) y Cetrolerelix (CETROTIDE®); al cuarto día del procedimiento de aspiración folicular presenta dolor pélvico intenso, disuria, deposiciones diarreicas, ecografía abdominal y vaginal evidencia líquido libre en cavidad alrededor de 1000cc, además de ovarios tanto derecho e izquierdo con volumen de 102 mL y 189 mL respectivamente. Paciente es ingresada para realizar tratamiento hidratación parenteral, Enoxaparina 40mg subcutánea, Cabergolina 0.5mg vía oral, alta a las 72 horas. DISCUSIÓN: Las claves para la prevención del síndrome de hiperestimulación ovárica son la experiencia con la terapia de inducción de la ovulación y el reconocimiento de los factores de riesgo para el síndrome de hiperestimulación ovárica. Los regímenes de inducción de la ovulación deberían ser altamente individualizados, monitorizados cuidadosamente y usando dosis y duración mínimas del tratamiento con gonadotropinas para conseguir la meta terapéutica. CONCLUSIONES: El síndrome de hiperestimulación ovárica constituye la complicación más temida durante el uso de inductores de la ovulación; el conocimiento de factores de riesgo, puede prevenir o evitar que llegue a ser de un caso severo, lo cual puede causar mayor morbilidad o hasta mortalidad. La vitrificación se convierte en la técnica que permite prevenir el síndrome de hiperestimulación ovárica, junto con esta técnica hay 2 alternativas: la inducción con análogo de la hormona liberadora de gonadotropina o el uso de agonistas dopaminérgicos.

INTRODUCTION: Ovarian hyperstimulation syndrome is an exaggerated response of the ovary to hormonal treatments to stimulate egg formation. OBJECTIVE: To describe the clinical case of a woman with ovarian hyperstimulation syndrome; to review the approach, management, treatment and how to prevent it. CLINICAL CASE: 37-year-old female patient, multigestation, under treatment with metformin for polycystic ovary syndrome, presenting infertility secondary to tubal factor, who developed a moderate picture of ovarian hyperstimulation syndrome as a consequence of the application of in vitro fertilization techniques (recombinant human follitropin alfa (GONAL-F®) and Cetrolerelix (CETROTIDE®); On the fourth day of the follicular aspiration procedure she presents intense pelvic pain, dysuria, diarrheic stools, abdominal and vaginal ultrasound shows free fluid in the cavity of about 1000cc, in addition to right and left ovaries with a volume of 102 mL and 189 mL respectively. Patient was admitted for parenteral hydration treatment, Enoxaparin 40mg subcutaneous, Cabergoline 0.5mg orally, discharged after 72 hours. DISCUSSION: The keys to prevention of ovarian hyperstimulation syndrome are experience with ovulation induction therapy and recognition of risk factors for ovarian hyperstimulation syndrome. Ovulation induction regimens should be highly individualized, carefully monitored, and using minimal doses and duration of gonadotropin therapy to achieve the therapeutic goal. CONCLUSIONS: Ovarian hyperstimulation syndrome constitutes the most feared complication during the use of ovulation inducers; knowledge of risk factors, may prevent or avoid it from becoming a severe case, which may cause increased morbidity or even mortality. Vitrification becomes the technique that allows preventing ovarian hyperstimulation syndrome, along with this technique there are 2 alternatives: induction with gonadotropin-releasing hormone analog or the use of dopaminergic agonists.

Cryopreservation as a strategy for prevention of ovarian hyperstimulation syndrome in a public assisted reproduction service in São Paulo - Brazil

SUMMARY OBJECTIVE: This study aimed to evaluate the prevalence of ovarian hyperstimulation syndrome (OHSS) and associated risk factors in patients undergoing fertilization cycles at risk of OHSS (≥15 antral follicles or ≥15 oocytes aspirated) and submitted to cryopreservation of all embryos in the Human Reproduction Service of the Pérola Byington Hospital (Referral Center for Women's Health) in São Paulo, SP, Brazil. METHODS: This cross-sectional, institutional, descriptive study of secondary data from patients' charts enrolled in the Assisted Reproduction Service of the Pérola Byington Hospital at risk of OHSS after controlled ovarian stimulation and submitted to cryopreservation of all embryos was conducted between January 2015 and September 2017. RESULTS: OHSS occurred in 47.5% of cycles, all with mild severity, and there were no moderate or severe cases of OHSS. CONCLUSION: The cryopreservation of all embryos is associated with a reduction in moderate and severe forms of OHSS. Risk factors for OHSS should be evaluated prior to initiation of treatment, with less intense stimulation protocols accordingly.

Aflibercept suppresses ovarian hyperstimulation syndrome: an experimental study in rats

SUMMARY OBJECTIVE: In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model. METHODS: A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth. RESULTS: Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively). CONCLUSION: Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.

Clinical characteristics of severe late-onset ovarian hyperstimulation syndrome and its impact on the live birth outcome of IVF-ET / 中华妇产科杂志

Objective:To investigate the correlation between different clinical features and live birth in patients with severe late-onset ovarian hyperstimulation syndrome (OHSS) after in vitro fertilization-embryo transfer (IVF-ET).Methods:The clinical information of 330 patients who were pregnant after IVF-ET and referred to medical treatments diagnosed as late-onset severe OHSS in Peking University Third Hospital from January 2016 to December 2020 was retrospectively analyzed. The patients were divided into live birth achieved group ( n=287) and non-live birth achieved group ( n=43) according to pregnancy outcomes, and live birth achieved group was further divided into two subgroups, full-term birth group ( n=222) and early-term birth group ( n=65) according to gestational week at delivery for better analysis. Single factor and multi-factor analysis were utilized to clarify the influencing factors of both live birth and early-term birth. Results:Among all the patients who received IVF-ET, the incidence of severe OHSS was 0.67% (673/100 758). Among 330 severe late-onset OHSS patients, 42.4% (140/330) had pleural effusion, the incidence of abnormal liver function was 69.4% (229/330), and the live birth rate was 87.0% (287/330). Among the 287 patients who achieved live birth, 55.4% (159/287) had no pleural effusion, 18.5% (53/287) had a small amount of pleural effusion, and 26.1% (75/287) had medium or massive pleural effusion; in the non-live birth achieved group, there were more patients without pleural effusion and less patients with a small amount of pleural effusion; the difference was statistically significant ( χ2=6.213, P=0.045). The rate of selective fetal reduction in live birth achieved group was 16.0% (46/287), which was significantly higher than that in the non-live birth achieved group, which was 2.3% (1/43; χ2=5.749, P=0.017). Multivariate logistic regression analysis revealed that moderately abnormal liver function was an independent risk factor for live birth ( OR=3.15, 95% CI: 1.60-6.19), while selective fetal reduction was an independent protective factor for live birth ( OR=0.13, 95% CI: 0.02-0.96). Additionally, subgroup analysis suggested that twin birth was an independent risk factor for preterm birth ( OR=8.54, 95% CI: 4.31-16.91). Conclusions:Moderate hepatic dysfunction may be associated with adverse pregnancy outcomes in patients with severe late-onset OHSS. Selective fetal reduction and singleton pregnancy are recommended to ameliorate live birth rate, full-term delivery rate, also the maternal and neonatal prognosis for patients with multiple pregnancies.

Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles / 中华妇产科杂志

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Sudden death of an egg donor during oocyte retrieval due to ovarian hyperstimulation syndrome

ABSTRACT Ovarian Hyperstimulation Syndrome (OHSS) is uncommon among oocyte donors during in vitro fertilization (IVF) procedure and is rarely associated with death. We report a case of a 23-year-old oocyte donor who suddenly died on the operation table during oocyte retrieval. She had no risk factors in her menstrual history, laboratory, or clinical parameters. The antagonist cycle, triggered with the GnRH agonist protocol, was carried out. The cause of death at autopsy was attributed to respiratory failure due to acute massive pulmonary edema, which developed due to the complication of OHSS. Only a few autopsy cases associated with OHSS have been published, but, as far as we know, no clinical or autopsy cases of sudden death caused by OHSS have been reported.

Qilin pills prevent ovarian hyperstimulation syndrome of patients after IVF-ET by regulating plasma-related indicators / 中国临床药理学与治疗学

AIM: To study the preventive effect of Qilin pill on ovarian hyperstimulation syndrome (OHSS) after in vitro fertilization and embryo transfer (IVF-ET) and its effects on vascular endothelial growth factor (VEGF), tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in plasma. METHODS: Sixty-four patients undergoing IVF-ET treated in our hospital from January 2016 to January 2019 were selected. On the day of ovulation induction injection of human chorionic gonadotropin (HCG), 32 patients with high risk factors of OHSS were randomly divided into two groups. The control group received western medicine therapy, while the observation group received extra Qilin pill. The incidence of mild to moderate OHSS, fresh cycle transplant cancellation rate, plasma VEGF, TF, TFPI levels, and clinical outcomes of patients undergoing IVF-ET (HCG positive rate, biochemical pregnancy rate, clinical pregnancy rate) were compared between the two groups.RESULTS:There was no severe OHSS occurred in the two groups, the incidence of OHSS in the observation group (12.50%) and the cancellation rate of fresh cycle transplantation (15.63%) were lower than those in the control group (50.00%, 43.75%)(χ2=6.063,P=0.014); The levels of VEGF and TF in the observation group on the day of egg retrieval and embryo transfer were [(368±103) pg/mL, (392±91) pg/mL],[(24±4)pg/ mL,(29±4) pg/mL], which were lower than the control group [(436±117) pg/mL, (448±108) pg/mL],[(26±4) pg/mL, (31±4) pg/mL] (t=2.450,2.237,4.093,5.204,P=0.017,0.029,<0.001,<0.001); The plasma TFPI levels in the observation group on the day of egg retrieval and embryo transfer were [(73±18) ng/mL,(66±12) ng/mL], higher than the control group [(62±16)ng/mL, (58±10) ng/mL](t=2.550,3.032,P=0.014,0.004); The biochemical pregnancy rate in the observation group (8.70%) was lower than that in the control group (42.86%) (χ2=4.147, P=0.042),the clinical pregnancy rate (91.30%) was higher than that of the control group (57.14%) (χ2=4.147,P=0.042).CONCLUSION:Qilin pill can prevent the occurrence of severe OHSS after IVF-ET, reduce the occurrence of mild to moderate OHSS, decrease the cancellation rate of fresh cycle transplantation and improve the pregnancy outcome after IVF-ET; Its mechanism may be related to the regulation of the expression of VEGF, TF and TFPI.

Letrozole versus gonadotropin-releasing hormone antagonist during luteal phase in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial / 中华妇产科杂志

Objective@#To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS).@*Methods@#A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group (n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group (n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured.@*Results@#There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48);P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval (P<0.05).@*Conclusion@#Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.

Freeze-all en reproducción asistida

Los avances en los protocolos de vitrificación y los resultados obtenidos tras la transferencia de embriones congelados han dado lugar a una versión distinta de los ciclos estándar de reproducción asistida: los ciclos freeze-all. Independientemente de su uso frente a las indicaciones más comunes (progesterona elevada, riesgo de hiperestimulación, entre otros), este nuevo concepto hoy representa una práctica habitual en muchas clínicas siendo aplicado a todas las pacientes. En este artículo analizaremos los distintos factores que pudieron haber contribuido a este cambio de política y la evidencia científica en relación al tema. Basados en esta evidencia concluiremos si las clínicas deberían cambiar su forma de trabajo pasando de transferencias de embriones frescos a solo transferencia de embriones congelados o si deberíamos mantener el protocolo estándar.

Breakthroughs in vitrification protocols and the results obtained after frozen embryo transfer have resulted in a different version of the assisted reproduction standard cycles: the "freeze-all" cycles. Regardless of their use beyond the usual indications (elevated progesterone, risk of hyperstimulation, among others), this new concept currently represents a common practice in many institutions and is applied to all patients. In this article, we will discuss the various factors that may have contributed to this change in policy and the scientific evidence for this topic. Based on this evidence, we will conclude if clinics should change their way of working from fresh embryo transfers to only transfer frozen embryos, or if we should maintain the standard protocol.

Early gonadotropin-releasing hormone antagonist protocol in women with polycystic ovary syndrome: A preliminary randomized trial / 대한생식의학회지

OBJECTIVE: To prospectively evaluate the efficacy and safety of a fixed early gonadotropin-releasing hormone (GnRH) antagonist protocol compared to a conventional midfollicular GnRH antagonist protocol and a long GnRH agonist protocol for in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). METHODS: Randomized patients in all three groups (early antagonist, n=14; conventional antagonist, n=11; long agonist, n=11) received 21 days of oral contraceptive pill treatment prior to stimulation. The GnRH antagonist was initiated on the 1st day of stimulation in the early antagonist group and on the 6th day in the conventional antagonist group. The GnRH agonist was initiated on the 18th day of the preceding cycle. The primary endpoint was the number of oocytes retrieved, and the secondary endpoints included the rate of moderate-to-severe ovarian hyperstimulation syndrome (OHSS) and the clinical pregnancy rate. RESULTS: The median total number of oocytes was similar among the three groups (early, 16; conventional, 12; agonist, 19; p=0.111). The early GnRH antagonist protocol showed statistically non-significant associations with a higher clinical pregnancy rate (early, 50.0%; conventional, 11.1%; agonist, 22.2%; p=0.180) and lower incidence of moderate-to-severe OHSS (early, 7.7%; conventional, 18.2%; agonist, 27.3%; p=0.463), especially among subjects at high risk for OHSS (early, 12.5%; conventional, 40.0%; agonist, 50.0%; p=0.324). CONCLUSION: In PCOS patients undergoing IVF, early administration of a GnRH antagonist may possibly lead to benefits due to a reduced incidence of moderate-to-severe OHSS in high-risk subjects with a better clinical pregnancy rate per embryo transfer. Further studies with more subjects are required.

Clinical outcomes of frozen embryo transfer cycles after freeze-all policy to prevent ovarian hyperstimulation syndrome

OBJECTIVE: To compare the clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in frozen embryo transfers (FETs) following either freeze-all policy to prevent ovarian hyperstimulation syndrome (OHSS; freeze-all group) or excess embryo cryopreservation after fresh embryo transfer (surplus group). METHODS: The freeze-all group comprised 44 FET cycles performed in 25 women between 2010 and 2016. The surplus group comprised 53 FET cycles performed in 47 women during the same period. The cumulative CPR and OPR according to duration of cryopreservation (interval between cryopreservation and FET) was estimated using Kaplan-Meier plots. Cox regression analysis was used for identifying factor to affect to cryopreservation duration in cycles with pregnancy. RESULTS: In day 2–4 transfer cycles, the crude CPR (40% vs. 18.2%) and OPR (20% vs. 4.5%) were similar between the 2 groups. In day 5 transfer, the crude CPR (33.3% vs. 38.7%) and OPR (33.3% vs. 29%) were also similar between the 2 groups. The cumulative CPR (100% vs. 47.5%) and OPR (100% vs. 33.3%) in day 2–4 transfer as well as the cumulative CPR (46.7% vs. 100%) and OPR (46.7% and 74.8%) in day 5 transfer were also similar between the 2 groups. The median duration of cryopreservation was significantly shorter in the freeze-all group than in the surplus group (19.8 vs. 36.9 weeks, P=0.04). Previous history of delivery was the only factor associated with a shorter cryopreservation duration in cycles with pregnancy (hazard ratio, 0.18; 95% confidence interval, 0.05–0.65; P=0.01). CONCLUSION: Freezing embryos to prevent OHSS and transferring the frozen embryos later may guarantee an acceptable reproductive outcome.

A retrospective analysis of the follicle-stimulating hormone starting dose in expected normal responders undergoing their first in vitro fertilization cycle: proposed dose versus empiric dose / 대한생식의학회지

OBJECTIVE: The purpose of this retrospective study was to evaluate the appropriateness of various follicle-stimulating hormone (FSH) starting doses in expected normal responders based on the nomogram developed by La Marca et al. METHODS: A total of 117 first in vitro fertilization cycles performed from 2011 to 2017 were selected. All women were expected normal responders and used a recombinant FSH and flexible gonadotropin-releasing hormone antagonist protocol. The FSH starting dose was empirically determined (150, 225, or 300 IU). The FSH starting dose indicated by La Marca's nomogram was determined using female age and serum anti-Müllerian hormone or basal FSH levels. If the administered dose was exactly the same as the proposed dose, the cycle was assigned to the concordant group (34 cycles). If not, it was assigned to the discordant group (83 cycles). Optimal ovarian response was defined as a total of 8–14 oocytes, hypo-response as 14 oocytes. RESULTS: Between the concordant and discordant group, ovarian response (optimal, 32.4% vs. 27.7%; hypo-response, 55.9% vs. 54.2%; and hyper-response, 11.8% vs. 18.1%) and the number of total or mature oocytes were similar. Ovarian hyperstimulation syndrome was rare in both groups (0% vs. 1.2%). The implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate were all similar. CONCLUSION: The use of the proposed FSH starting dose determined using La Marca's nomogram did not enhance the optimal ovarian response rate or pregnancy rate in expected normal responders. Individualization of the FSH starting dose by La Marca's nomogram appears to have no distinct advantages over empiric choice of the dose in expected normal responders.

Desencadenantes de la maduración ovocitaria en ciclos de fecundación in vitro / Triggers of oocyte maturation in cycles of in vitro fertilization

Tradicionalmente, desde que se iniciaron las técnicas de reproducción asistida, se solía usar un bolo de 5 000-10 000 UI de gonadotropina coriónica humana para la maduración final de los ovocitos como método estándar. Recientemente, se ha introducido un nuevo concepto, en el que los agonistas de la hormona liberadora de gonadotropina juegan un papel esencial en este campo. Ofrece importantes ventajas, entre las que se incluyen: una virtual prevención completa del síndrome de hiperestimulación ovárica. No obstante, algunos estudios defienden que el uso de hormona liberadora de gonadotropina puede ocasionar un defecto en la fase lútea que puede finalizar en una disminución en las tasas de implantación, en las tasas de gestación clínica o en un aumento de las tasas de aborto precoz. Así pues, en esta revisión analizamos las diferentes opciones terapéuticas para desencadenar la maduración final de los ovocitos en las técnicas de reproducción asistida, y discutimos los riesgos, beneficios y posibles complicaciones del uso de los agonistas de la GnRH como inductor de ovulación en ciclos de fecundación in vitro/inyección intracitoplasmática de espermatozoides(AU)

Traditionally, a bolus of 5000-10000 IU human chorionic gonadotropin (hCG) was used for final follicular maturation and ovulation as a standard method since assisted reproduction techniques started (ART). Recently, a new concept in which the releasing gonadotropin hormone agonists (GnRH-a) play an essential role has been introduced. This offers important advantages, including virtually prevention of ovarian hyperstimulation syndrome (OHSS). However, some studies described that using GnRH-a, could lead to defects in the luteal-phase that may result in a reduction of the implantation and clinical pregnancy rates; and also in an increase of early abortion rates. Therefore, the aim of this review is the analysis of different pharmaceutical options to trigger final oocyte maturation in ART, and the discussion of the risks, benefits and likely complications associated with the use of GnRH-a as an inductor of the ovulation during in vitro fecundation/intracitoplasmatic sperm injection cycles (IVF/ICSI)(AU)

Clinical analysis of 77 cases with ovarian hyperstimulation syndrome / 上海交通大学学报（医学版）

Objective·To discusses the high risk factors and therapy strategies for ovarian hyperstimulation syndrome (OHSS). Methods·Seventy-seven cases with moderate and severe OHSS were collected to be retrospectively analyzed in Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2016. Results·Compared with non-pregnant patients, pregnant patients were more likely to have severe OHSS (P<0.05). Embryo transfer patients who underwent ovulation induction and oocyte retrieval became severe OHSS much more easily and had a much longer hospital stay than oocyte retrieval patients (P<0.05). Pumping ascites and pleural effusion or not has no effect on the length of hospital stay and the usage of low molecular dextran for patients with severe OHSS. Conclusion·The risk of OHSS should be evaluated to determine whether or not to carry out a fresh embryo transfer in patients who underwent ovulation induction and oocyte retrieval. For OHSS patients who have undergone embryo transfer or pregnancy, more attention should be paid to the progress of the disease, and individualized treatment is required.

Application of Orem’ self-care theory in patients with a tendency of ovarian hyperstimulation syndrome / 第二军医大学学报

Objective To investigate the performance of Orem’ sef-care theory application in the patients with a tendency of ovarian hyperstimulation syndrome (OHSS). Methods A total of 307 patients with a tendency of progressing OHSS, who were treated in Reproductive Medicine Center of Changhai Hospital of Second Military Medical University from Oct 2015 to Oct 2016, randomly received routine nursing management in combination with Orem’ sel--care theory (Orem’ sel--care theory group, n=165) or routine nursing management (routine group, n=142). The incidence and severity of OHSS of the patients in the two groups were compared and analyzed. Results Sixty-eight of 307 OHSS tendency patients finally developed OHSS, with 38 in the routine group (16 mild OHSS, 18 moderate and four severe), and 30 in the Orem’ sef-care theory group (20 mild, nine moderate and one severe). There was no significant difference in OHSS incidence between the two groups (P>0. 05); while the reduction of OHSS severity in the Orem’ sef-care theory group was more obvious than that in the routine group, and the difference was statistically significant (P<0. 05). Conclusion Orem’ sef-care theory nursing management has an advantage in reducing the severity of OHSS over routine nursing and is worthy of clinical use.

Association between follicular output rate and clinical outcome in patients with polycystic ovarian syndrome / 实用医学杂志

Objective To find the association between follicular output rate and clinical outcome in patients with polycystic ovarian syndrome (PCOS).Methods A total of 285 female patients with PCOS who were undergoing in vitro fertilization-embryo transfer (IVF-ET) for the first time were included in the study and were divided into three groups according to follicular output rate (FORT) values.The general information,the parameters of the controlled ovarian hyperstimulation,and clinical outcomes were compared.Results The concentration of serum E2 on the day of HCG,preovulatory follicle count (PFC),the number of retrieved oocytes,good-quality embryo rates,clinical pregnancy rate decreased sequently in groups with high,mediate and low FORT value.The incidence of moderate and severe ovarian hyper-stimulation syndrome (OHSS) in the group with mediate FORT value was significantly lower than that of groups with high and low FORT value.The incidence of severe OHSS in 3 groups with high,mediate and low FORT value was 20.6％,9％ and 17.8％ respectively and the difference was statistically significant (P =0.037).Conclusions The value of FORT may predict the clinical outcome of IVF/ ICSI-ET in patients with PCOS.Effort should be made to prevent OHSS in PCOS patients with high or low FORT value in their controlled ovarian hyperstimulation cycles.

Ultrasound forecast model of ascites volume in patients with ovarian hyperstimulation syndrome:Establishment and validation / 中国医学影像技术

Objective To establish and validate the ascites volume forecast model of ascites puncture drainage operation with ultrasound measuring for 6 positions in patients with ovarian hyperstimulation syndrome (OHSS),including front of the uterus,Douglas pouch,right iliac fossa,left iliac fossa,hepatorenal recess and spleen kidney fossa.Methods Fifty patients received ultrasonographic measurement (measurement group) and then underwent ascites puncture drainage operation within 6 h.Three scatter diagrams of actual ascites volume (Y;ml) and key position ascites depth summation (X;mm),height correlation coefficient and surface area correlation coefficient were drawn.The simple and practical regression equation with better correlation was used to be the one verified.Then 100 subsequently HSS patients were enrolled in verrification group.Forecast ascites volume calculated with above-mentioned regression equation and actual ascites volume was analyzed with Bland-Altm an method and paired t test.Results Regression equation obtained with the scatter diagram was Y=-256.554 + 10.452X (R2 =0.577),which could be simplified as Y=10.5X-250.0.The limit of consistency between forecast ascites volume and actual ascites volume was (-1 314.02,1 560.48) ml,and the bias was 123.23 ml.The difference between forecast ascites volume and actual ascites volume was not statistically significant (t=-1.684,P=0.096).Conclusion The simplified equation is Y=10.5X-250.0 to forecast ascites volume caused by OHSS,therefore guiding clinical work.

Effect of Yiqixue Buganshen Recipe on the level of serum VEGF in high-risk patients with ovarian hyper- stimulation syndrome / 实用医学杂志

Objective To investigate the clinical effect of the Yiqixue Buganshen Recipe(YBR)on the level of serum VEGF in high-risk patients with OHSS. Method 298 infertile women with high-risk OHSS in the reproductive centre of our hospital from June to November ,2016 were enrolled into the traditional Chinese medicine (TCM) group (n = 148) and the control group(n = 150). 145 infertile women without high-risk OHSS were enrolled into the normal group. All the patients received the long protocol treatment ,and patients in the TCM group received the YBR treatment. Results Patients have higher quality embryo rate ,lower moderate and more severe OHSS rate in the TCM group compared with the control group(P<0.05). Patients in the normal group have lower serum VEGF compared with patients in the other 2 groups on the all three days. Patients in the TCM group has lower serum VEGF on the day of embryo transfer compared with patients in the control group(P<0.05). Conclusions The increment of the serum VEGF level is closely related to OHSS. The YBR may reduce the rate of moderate and severe OHSS by reducing the serum VEGF level on the day of embryo transfer ,which may prevent the moderate and severe OHSS of the high-risk patients.

Gonadotropin releasing hormone antagonist administration for treatment of early type severe ovarian hyperstimulation syndrome: a case series

OBJECTIVE: To report an efficacy of gonadotropin releasing hormone (GnRH) antagonist administration after freezing of all embryos for treatment of early type ovarian hyperstimulation syndrome (OHSS). METHODS: In 10 women who developed fulminant early type OHSS after freezing of all embryos, GnRH antagonist (cetrorelix 0.25 mg per day) was started at the time of hospitalization and continued for 2 to 4 days. Fluid therapy and drainage of ascites was performed as usual. RESULTS: Early type OHSS was successfully treated without any complication. At hospitalization, the median (95% confidence interval [CI]) of the right and the left ovarian diameter was 10.0 cm (7.6 to 12.9 cm) and 8.5 cm (7.5 to 12.6 cm). After completion of GnRH antagonist administration, it was decreased to 7.4 cm (6.2 to 10.7 cm) (P=0.028) and 7.8 cm (5.7 to 12.2 cm) (P=0.116), respectively. The median duration of hospital stay was 6 days (3 to 11 days). Trans-abdominal drainage of ascites was performed in 2 women and drainage of ascites by percutaneous indwelling catheter was performed in 4 women. No side effect of GnRH antagonist was noted. CONCLUSION: GnRH antagonist administration appears to be safe and effective for women with fulminant early type OHSS after freezing all embryos. Optimal dose or duration of GnRH antagonist should be further determined.

Síndrome de hiperestimulación ovárica severo: Informe de caso y revisión de literatura / Severe Ovarian Hyper Stimulation Syndrome: Case Report and Literature Review / Síndrome de hiperestimulação ovárica grave: Relato de caso e revisão da literatura

Introducción: El síndrome de hiperestimulación ovárica severo es la complicación más grave de la estimulación ovárica durante la inducción de la ovulación. Los hallazgos característicos son la presencia de ovarios aumentados de volumen y ascitis en relación a extravasación de líquido por aumento de la permeabilidad capilar, cuya severidad puede llevar a falla respiratoria, renal, colapso hemodinámico y eventos tromboembólicos. Objetivo: Describir un caso clínico de síndrome de hiperestimulación ovárica, junto con una revisión de la literatura sobre la patología, orientada al diagnóstico y tratamiento óptimo de pacientes con estas características clínicas. Presentación del caso: Paciente de 29 años con antecedente de síndrome de ovario poliquístico que presenta síndrome de hiperestimulación ovárica severo como complicación secundaria a estimulación gonadotrófica. El cuadro clínico mostró ovarios aumentados de tamaño en la evaluación sonográfica; anasarca dada por ascitis y derrames pleurales bilaterales e insuficiencia respiratoria tipo distrés respiratorio del adulto. Se realizó paracentesis y se utilizó ventilación mecánica no invasiva, logrando la expansión pulmonar. Discusión: El análisis de este caso se inició siete días después de la administración de gonadotropina, favorecido por las condiciones previas de la paciente, sin complicaciones letales. Conclusiones: La paracentesis puede constituir una opción terapéutica efectiva en el tratamiento de ascitis con compromiso de la función pulmonar. La ventilación mecánica no invasiva es una estrategia para evitar la intubación en estas pacientes lo cual evita los periodos de sedación exhaustivos y el consiguiente riesgo de broncoaspiración. [Urbina-Contreras ZE, Urbina-Echeverry SE,Lamos-Duarte AF, Picón-Jaimes YA. Síndrome de hiperestimulación ovárica severo: Informe de caso y revisión de literatura. MedUNAB 2017; 20(2): 244-251].

Introduction: Severe ovarian hyper stimulation syndrome is the most serious complication of ovarian stimulation during the induction of ovulation. Characteristic findings are the presence of increased ovarian volume and ascites in relation to fluid extravasation due to increased capillary permeability whose severity can lead to respiratory failure, renal failure, and hemodynamic collapse and thromboembolic events. Objective: To describe a clinical case of OHSS, along with a review of the literature on the pathology, aimed at the diagnosis and optimal treatment of patients with these clinical characteristics. Case presentation: A 29-year-old patient with a history of polycystic ovarian syndrome who presented severe Severe ovarian hyper stimulation syndrome as a secondary complication to gonadotrophic stimulation. The clinical profile showed enlarged ovaries in the sonographic test; anasarca due to ascites and bilateral pleural effusions and respiratory failures that belong to a respiratory distress type in this adult patient. Paracentesis was performed and noninvasive mechanical ventilation was used, achieving lung expansion with it. Discussion: The analysis of this case was started seven days after the administration of gonadotropin, favored by the patient's previous conditions, with no lethal complications. Conclusions: Paracentesis may be an effective therapeutic option in the treatment of ascites with compromised lung function. Noninvasive mechanical ventilation is a strategy to avoid intubation in these patients, which avoids the periods of exhaustive sedation and the consequent risk of bronchoaspiration. [Urbina-Contreras ZE, Urbina-Echeverry SE, Lamos-Duarte AF, Picón-Jaimes YA. Severe Ovarian Hyper Stimulation Syndrome: Case Report and Literature Review. MedUNAB 2017; 20(2): 244-251].

Introdução: O síndrome de hiperestimulação ovárica avançado é a complicação mais grave da estimulação ovariana durante a indução da ovulação. As características achadas são o aumento do volumem dos ovários e ascite em relação ao extravasamento do fluido devido ao aumento da permeabilidade capilar, cuja gravidade pode levar à insuficiência respiratória, insuficiência renal,colapso hemodinâmico e eventos tromboembólicos. Objetivo: Descrever um caso clínico de síndrome de hiperestimulação ovárica avançado, juntamente com uma revisão da literatura sobre a patologia, visando o diagnóstico e tratamento ótimo de pacientes com essas características clínicas. A presentação do caso: Paciente de 29 anos com história de síndrome de ovário policístico que apresenta síndrome de hiperestimulação ovárica avançado como complicação secundária à estimulação gonadotrófica. O quadro clínico mostrou ovários ampliados na avaliação ultra-sonográfica; anasarca devido à ascite e derrames pleurais bilaterais e insuficiência respiratória do tipo insuficiência respiratória do adulto. Foi realizada a paracentese e foi utilizada ventilação mecânica não invasiva, atingindo a expansão pulmonar. Discussão: A análise deste caso começou sete dias após a administração da gonadotrofina, favorecida pelas condições prévias da paciente, sem complicações letais. Conclusões: A paracentese pode constituir uma opção terapêutica efetiva no tratamento de ascite com comprometimento da função pulmonar. Aventilação mecânica não invasiva é uma estratégia para evitar intubação nessas pacientes, o que evita os períodos de sedação exaustiva e o consequente risco de bronco-aspiração. [Urbina-Contreras ZE, Urbina-Echeverry SE, Lamos-Duarte AF, Picón-Jaimes YA. Síndrome de hiperestimulação ovárica grave: Relato de caso e revisão da literatura. MedUNAB 2017; 20(2): 244-251].