Severe Ovarian Hyperstimulation Syndrome Research Articles

Letrozole and ovarian hyperstimulation syndrome: Retrospective cross-sectional study

Background: Recently, letrozole has been used to prevent moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology cycles due to its estrogen-reducing and androgen-increasing effects on the ovaries, affecting granulosa cells, and reducing vascular endothelial growth factor production. Objective: This study aimed to investigate the impact of letrozole consumption in preventing OHSS in infertile women with polycystic ovarian syndrome undergoing in vitro fertilization. Materials and Methods: In this cross-sectional study, among 1743 medical records of infertile women who were scheduled for oocyte retrieval at Research and Clinical Center for Infertility, Yazd, Iran. Data of 343 women with polycystic ovarian syndrome diagnosis and at risk of OHSS was extracted from March 2022–2023. The stimulation was carried out using a flexible gonadotropin releasing hormone (GnRH) antagonist protocol. Women were divided into 2 groups based on whether they received letrozole or not. In the letrozole group, 2.5 mg letrozole twice daily was continued from the trigger day, while in the control group, women did not receive letrozole. The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription were analyzed. Results: 89 women in the letrozole and 254 women in the control group were examined. There was no statistically significant difference between groups in terms of age and body mass index; however, anti-Mullerian hormone was significantly higher than control group (7.53 ± 4.61 vs. 5.47 ± 3.63, p < 0.001). The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription showed no significant differences between the groups. Conclusion: Recent study indicates that incorporating letrozole into the treatment of GnRH antagonists and cabergoline does not reduce the OHSS severity. Key words: Letrozole, Polycystic ovary syndrome, Ovarian hyperstimulation syndrome, Assisted reproductive technologies.

The dark side of random-start ovarian stimulation: OHSS due to inadvertent pregnancy

Research QuestionCan inadvertent pregnancies go unnoticed when initiating random-start ovarian stimulation (RSOS) despite monitoring? DesignCase series at the university-based tertiary-care fertility clinic. ResultsBetween June 2022 and December 2023, two cases of undetected early pregnancy at the onset of random-start ovarian stimulation were identified, both leading to severe ovarian hyperstimulation syndrome (OHSS) with hospitalization. ConclusionRSOS protocols add flexibility in fertility clinics when there is no intention of a fresh embryo transfer but may be associated with insidious risk of OHSS. We advocate for comprehensive consultation and serial monitoring of human chorionic gonadotropin (hCG) during stimulation while cautioning against overreliance on baseline hormone levels when initiating RSOS. If the benefits of RSOS seem limited, healthcare providers should consider delaying the stimulation to avert health, but also medicolegal, and financial complications.

Abstract 134: Thrombotic Complications of Ovarian Hyperstimulation Syndrome

Introduction: Ovarian hyperstimulation syndrome (OHSS) is a well-known complication of ovarian stimulation used during assisted reproductive technology cycles. In severe OHSS, increases in capillary permeability can result in hemoconcentration and hypercoagulability leading to thrombotic events, including stroke and cerebral venous thrombosis. Herein we sought to determine the prevalence of hospitalization for thrombotic events shortly after OHSS using population-level data. Methods: We conducted two separate retrospective cohort studies of patients with OHSS using publicly available datasets: (1) administrative claims data from the Healthcare Cost and Utilization Project (HCUP) across 11 states from 2016 to 2020 and (2) National Inpatient Sample (NIS) registry data from the end of 2015 to 2020. HCUP contains both emergency department and inpatient encounters whereas NIS contains a nationally representative sample of inpatient encounters. For our study, all female patients with an encounter for OHSS, defined using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) code N98.1 were included from each dataset. Our primary study outcome was any stroke or major thrombotic event identified within 60 days of OHSS diagnosis in HCUP or during the index admission for OHSS in NIS. We used previously validated ICD-10-CM codes for acute ischemic stroke, intracerebral and subarachnoid hemorrhage, cerebral venous thrombosis, acute myocardial infarction, pulmonary embolism, and acute deep venous thrombosis to define our study outcome. Results: We identified a total of 747 patients with OHSS in HCUP. Within the HCUP cohort, fewer than 10 patients (<1%) were hospitalized with a stroke or thrombotic event within 60 days of OHSS diagnosis. There were 1,955 hospitalizations for OHSS in NIS. There were 20 (1%) pulmonary embolisms and 35 (1.8%) acute deep venous thromboses, but no other stroke/thrombotic complications in NIS. Conclusions: We found very few thrombotic events shortly after OHSS diagnosis using two large datasets. The low rate of outcome events after OHSS seen in each of our population-level analyses increases the reliability of these study results.

Early severe ovarian hyperstimulation syndrome (OHSS) - case report

Early severe ovarian hyperstimulation syndrome (OHSS) - case report

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Efficacy and safety of follitropin delta versus follitropin alpha/beta in infertility treatment: A systematic review and meta-analysis.

Follitropin δ may be an alternative to conventional follitropin α/β for controlled ovarian stimulation (COS) within assisted reproductive treatment (ART), but its efficacy and safety remain unknown. We performed a random-effects meta-analysis to compare the efficacy and safety of follitropin δ and follitropin α/β. We searched randomized controlled trials comparing follitropin δ and follitropin α/β using MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO-ITCRP on December 14, 2022. The primary outcomes were the live birth rate and the incidence of moderate or severe ovarian hyperstimulation syndrome (OHSS). The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation approach. The protocol was registered on the Open Science Framework. Three studies involving 2682 participants were included in our meta-analysis. The results indicated that follitropin δ may result in little to no difference in live birth rates (risk ratio [RR], 1.12; 95% confidence interval [CI], 0.91-1.38; low certainty) and the incidence of moderate or severe OHSS (RR, 0.78; 95% CI, 0.48-1.26; low certainty) compared with follitropin α/β. Follitropin δ may result in little to no difference in COS compared with follitropin α/β, especially in terms of live births and safety.

Prevention of moderate and severe ovarian hyperstimulation syndrome: a guideline

Ovarian hyperstimulation syndrome is a serious complication associated with assisted reproductive technology. This systematic review aims to identify who is at high risk for developing ovarian hyperstimulation syndrome, along with evidence-based strategies to prevent it and replaces the document of the same name last published in2016.

10252-COT-27 TWO CASES OF OVARIAN HYPERSTIMULATION SYNDROME IN A YOUNG FEMALE PATIENTS WITH GLIOMA WHO UNDERWENT OOCYTE CRYOPRESERVATION.

Abstract Young women with malignant gliomas may wish to have their oocytes preserved prior to the start of chemotherapy in order to maintain fertility. In such cases, fertility drugs make it possible to mature and retrieve multiple oocytes in the ovaries. However, the ovaries may overreact and mature many oocytes at once, resulting in adverse symptoms such as abnormal swelling of the ovaries, abdominal discomfort and pain, nausea and vomiting, abdominal distention, fluid retention (edema), and difficulty breathing. This is called ovarian hyperstimulation syndrome (OHSS), in which excessive secretion of estradiol associated with multiple follicle development leads to excessive production of VEGF, which rapidly increases the vascular permeability of systemic organs, resulting in a fluid shift into the third space, which is thought to cause ascites and pulmonary edema. In severe cases, intravascular dehydration and decreased circulating plasma volume can cause hypotension and oliguria, and the increased coagulation capacity associated with hemoconcentration can cause serious thrombotic complications. The severity of OHSS is classified into three levels: mild, moderate, and severe, based on four findings: subjective symptoms, the amount of pleural effusion, the degree of ovarian enlargement (ovarian diameter), and blood test findings. Early detection and appropriate management are essential. We have had two cases of OHSS, one of which was moderate and resolved successfully, while the other became severe, and we had to postpone the start of radiotherapy for a week longer than planned. Severe OHSS is a medical complication that neurosurgeons rarely encounter, and we report this case with a literature review.

Prevention of OHSS

Ovarian hyperstimulation syndrome (OHSS), perhaps the most serious complication arising from in vitro fertilization (IVF), is rare but life-threatening in some cases. In this lecture, we will first delve into the pathophysiology of OHSS and hallmark features such as hemoconcentration, hypercoagulability, electrolyte imbalances, fluid loss into third space, and renal insufficiency. In addition, clinical vignettes will illustrate some of the most severe cases of OHSS. Next, various methods for identifying patients at high risk of OHSS will be discussed. Available literature indicates that younger age and polycystic ovarian syndrome (PCOS) may be associated with the incidence of OHSS. Ovarian reserve markers such as anti-müllerian hormone (AMH) and antral follicle counts (AFC) have been suggested as useful screening tools. Also, stimulation cycle profiles, such as developing multiple follicles, peak serum estradiol levels, and the number of retrieved oocytes, may aid in identifying those at high risk. To lower the incidence of OHSS, modifying controlled ovarian stimulation (COS) protocols is essential. Evidence suggests that gonadotropin-releasing hormone (GnRH) antagonist protocol is beneficial in reducing the risk of OHSS. Medications such as dopamine agonists, aspirin, and metformin may be associated with lower risk while using clomiphene citrate remains controversial. “Coasting,” which is holding gonadotropins for several days to decrease the OHSS risk, has been suggested as another strategy. Triggering could be done differently using a GnRH agonist. Cycle segmentation by cryopreserving oocytes and embryos is also a feasible option. Close monitoring and early detection of symptoms are essential for prompt intervention and management of OHSS. By implementing preventative measures and closely monitoring patients, physicians may reduce the incidence and severity of OHSS and ensure safer fertility treatments.

#86 : Use of Triptorelin Versus Human Chorionic Gonadotropin as Ovulation Trigger

Background and Aims: Gonadotropin releasing hormone agonist (GnRH-a) trigger has been shown to be associated with significantly lower risk of moderate or severe ovarian hyperstimulation syndrome (OHSS) when compared among women at high risk of OHSS. However, trigger failure has been shown to occur in 2% of cycles using GnRH-a as trigger. This study aims to review the use of GnRH-a as ovulation trigger. Method: Retrospective review of records in antagonist cycles from an ART unit in a tertiary hospital from 2017-2021 was performed. Follicles were considered mature when they reach [Formula: see text] 15 mm. Ovulation triggered with urinary human chorionic gonadotropin (uhCG) (5000-10000 IU), recombinant hCG (rhCG) 250 mcg, or triptorelin 0.2 mg when there were [Formula: see text] 3 mature follicles. All embryos obtained from cycles using triptorelin were cryopreserved. Outcome including the number of oocytes retrieved, the follicle to oocyte index, ovarian hyperstimulation syndrome were reviewed. Results: 1378 cycles were included. 1089 cycles had uhCG or rhCG as trigger, while 284 cycles had triptorelin as trigger. Women in the triptorelin group were significantly younger with a lower basal follicle stimulating hormone level and a higher antral follicle count (Table 1). In the triptorelin group, the total number of mature sized follicles, estrogen level at trigger, oocytes retrieved, number of blastocysts were significantly higher compared to the hCG group (Table 2). Follicle to oocyte index was significantly higher in the triptorelin group but the proportion of mature oocytes were similar in both groups. There were no cases of trigger failure and OHSS in the triptorelin group, but 30 cases of OHSS, with18 cases early onset, 12 cases late onset, amongst them 10 cases (1%) were severe OHSS) in the hCG group. Conclusion: GnRH-a trigger is a good candidate as ovulatory trigger in women at risk of OHSS without hampering the laboratory outcome.

#20 : Follitropin Delta Can Play a Good Role in Both Patients with High Serum AMH Level and Patients with Low Serum AMH Level in IVF

Background and Aims: To evaluation clinical efficacy of follitropin delta in IVF procedure for Korean. Method: This is a prospective study performed by single physician at primary fertility center. From December 2020 to November 2021, total 82 cycles of IVF were performed. 70% of total cycles was performed using gonadotrophic releasing hormone (GnRH) antagonist protocol, and another 30% of cycles were gonadotrophin releasing hormone agonist (GnRHa) protocol. Results: Average duration of infertility was 2.2± 1.5 years. AMH levels were 2.4± 2.4 ng/ml. The number of obtained oocytes were 8.9± 5.0. Mean daily dose of follitropin delta were 10.3± 2.5 mcg, and total dosage were 121.8± 25.5 mcg. Duration of stimulation were 9.9± 2.0 days. Biochemical pregnancy rate was 38% and clinical pregnancy rate was 27%. No cases of severe ovarian hyperstimulation syndrome were developed. Conclusion: For both patients with good ovarian reserve, and the patients with poor ovarian reserve, follitropin delta can play a good role. With its discriminative fixed dosing protocol, follitropin delta gives more convenient way for both physicians and patients with minimal risk of OHSS, without having detrimental effect on pregnancy rate.

#74 : Rare Presentation of Bilateral Haemorrhagic Pleural Effusions in Ovarian Hyperstimulation Syndrome

Background and Aims: Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of controlled ovarian hyperstimulation. Pleural effusions seen in OHSS usually are accompanied by marked ascites. Isolated pleural effusion without ascites is extremely rare. Here, we report a case of severe OHSS with rare presentation of isolated bilateral haemorrhagic pleural effusions following controlled ovarian hyperstimulation in in vitro fertilization (IVF). Method: We present a case of a 31-year-old lady with polycystic ovarian syndrome (PCOS) undergoing IVF where antagonist regime was used. To reduce OH SS risk, agonist trigger was given followed by cryopreservation. The patient was discharged well after oocyte retrieval. She needed admission the following day due to worsening abdominal pain. Cabergoline was started together with analgesia. On day 4 admission, she developed left haemorrhagic pleural effusion which was drained. Her condition improved initially but pleural effusion recurred after a few days and this time was bilateral. Pleural fluid drainage was repeated. Results: Patient recovered and was discharged well after 3 weeks of hospitalization. Five months later, we performed frozen embryo transfer where two day-3 embryos were transferred (both 8-cell Grade 1). She had a successful singleton pregnancy. At 38 weeks of gestation, she delivered a healthy boy weighing 3.67 kg via Caesarean section. Conclusion: Pleural effusion as sole presentation of severe OHSS is a very rare occurrence. Despite close monitoring during ovarian stimulation and rigid guidelines, OHSS still occurs. Early detection and prompt intervention by a multidisciplinary team are crucial to ensure successful management of this serious complication.

Cocktail treatment by GnRH-antagonist, letrozole, and mifepristone for the prevention of ovarian hyperstimulation syndrome: a prospective randomized trial

Objective This study is aimed to determine the efficacy of a cocktail style treatment by combining GnRH-antagonist, letrozole, and mifepristone on the prevention of ovarian hyperstimulation syndrome (OHSS) in high-risk women. Methods This prospective, randomized controlled clinical trial was performed between January 2018 and December 2018. A total of 170 women who identified as high risk of OHSS during the ovarian hyperstimulation and underwent cryopreservation of whole embryos. On the day of oocyte retrieval, the combination group received 0.25 mg Cetrorelix for 3 d, 5 mg letrozole for 5 d, and 50 mg mifepristone for 3 d, the mifepristone group received 50 mg mifepristone for 3 d. A total of 156 cases were included in final analysis. All the frozen embryo transfer (FET) cycles were followed up until December 2021. Results The combination group showed significantly decreased incidence of moderate and severe OHSS than mifepristone group (20.5% vs. 42.3%), with remarkably reduced serum estradiol level on hCG + 3 and + 5 d, decreased ovarian diameter, and shortened luteal phase. Oocyte retrieval number, levels of estradiol on hCG + 0 and VEGF, and ovarian diameter on hCG + 5 were associated with the severity of the symptoms. There was no significant difference in cumulative live birth rates (LBRs) between the combination and mifepristone group (74.4% vs. 76.9%). Conclusions The combination treatment effectively reduces the incidence of moderate/severe OHSS in high-risk women.

Clinical Features of Severe Ovarian Hyperstimulation Syndrome with Hydrothorax.

Does the presence of hydrothorax suggest that severe ovarian hyperstimulation syndrome (OHSS) is associated with more severe conditions and worse pregnancy outcomes? The clinical data for 868 hospital patients with severe OHSS following IVF-ET at Peking University Third Hospital between 1 January 2016 and 21 July 2021 were retrospectively analysed. The patients were divided into two groups, the ascites alone group (n = 417) and the ascites combined with hydrothorax group (n = 451), to investigate the clinical features and pregnancy outcomes of patients with severe ovarian hyperstimulation syndrome (OHSS) combined with hydrothorax plus ascites. The clinical data for 868 hospital patients with severe OHSS following IVF-ET were included. A total of 51.96% of patients with severe OHSS had hydrothorax plus ascites, mainly bilateral and moderate hydrothorax. Most cases with hydrothorax could be monitored and observed, and only 2.66% of the cases required thoracentesis and pleural drainage. Clinically, the time to visit due to worsening symptoms was longer; the hospital stay was shorter; and the OHSS-related laboratory tests, such as white blood cells (WBC), haematocrit (HCT), and ovarian diameter, were less severe in the ascites combined with hydrothorax group than in the ascites alone group. For live-birth outcomes of IVF-ET, the presence and the volume of hydrothorax were not independent risk factors, while the late onset of OHSS (odds ratio [OR]: 0.857 95% confidence interval [CI]: 0.795, 0.925) and a history of foetal reduction (OR: 13.796 95% CI: 1.808, 105.288) were independent protective factors for live birth. Patients with severe OHSS combined with hydrothorax plus ascites have less severe clinical manifestations and laboratory tests than those with ascites alone. The presence and the volume of hydrothorax are unrelated to live-birth outcomes following in vitro fertilization and embryo transfer (IVF-ET).

Efficacy of progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization: a systematic review and meta-analysis.

NPLASY (202340059). https://inplasy.com/inplasy-2023-4-0059/.

Beyond the Umbrella: A Systematic Review of the Interventions for the Prevention of and Reduction in the Incidence and Severity of Ovarian Hyperstimulation Syndrome in Patients Who Undergo In Vitro Fertilization Treatments.

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for the prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analyses of randomized controlled trials (RCTs) and assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identified, analyzed in terms of safety/efficacy ratio and risk of bias, and graded using the Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In the IVF population not at a high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of a GnRH antagonist may reduce OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have been shown to be promising.

Guideline No. 315: Prevention of Ovarian Hyperstimulation Syndrome

Summary Statements1.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) Recommendations1.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)

P-645 standard- and low-dose dual trigger compared with human chorionic gonadotropin trigger in preimplantation genetic testing cycles

Abstract Study question Standard-dose dual trigger (SDT) and low-dose dual trigger (LDT) could improve the number of oocytes, blastocysts and euploid blastocysts or not compared with hCG trigger. Summary answer LDT increased the number of oocytes and blastocysts but not euploid blastocysts among high ovarian responders, while SDT cannot help poor to normal ovarian responders. What is known already For low and normal responders, hCG trigger was recommended by the ESHRE guidelines for ovarian stimulation for in vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) in 2020. For high responders, this guideline recommended gonadotropin-releasing hormone agonist (GnRH-a) as the first-choice treatment. While recent studies showed that SDT could increase the number of oocytes and blastocysts to achieve equivalent or better pregnancy outcomes among poor and normal ovarian responders. And LDT was designed to prevent severe ovarian hyperstimulation syndrome (OHSS) while guaranteeing embryo quality among high responders by previous studies. Study design, size, duration This retrospective cohort study was performed at the Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital from July 2018 to December 2021. A total of 2,649 IVF-PGT cycles involving 2,275 patients were analyzed, of which 2,270 cycles had complete baseline data. A total of 1,131, 715, and 424 cycles were included in the hCG trigger, SDT, and LDT groups, respectively. Participants/materials, setting, methods Patients who were triggered by SDT(triptorelin acetate 0.2 mg and rhCG 250 µg), LDT(triptorelin acetate 0.2 mg and rhCG 125 µg or hCG 2,000 IU), and hCG (rhCG 250 µg) with GnRH-antagonist stimulation protocol in IVF-PGT cycles were enrolled. The number of oocytes retrieved, blastocysts, and euploid blastocysts were compared as primary endpoints. Propensity score matching (PSM) was used to control for confounding factors of retrospective study. Main results and the role of chance The SDT and hCG groups had a comparable number of oocytes retrieved (11.0 [7.0, 16.0] vs. 11.0 [7.0, 15.0], p = 0.580), blastocysts (2.0 [1.0, 3.0] vs. 2.0 [1.0, 3.0], p = 0.517), and euploid blastocysts (1.0 [0.0, 2.0] vs. 1.0 [0.0, 2.0], p = 0.383) after PSM. LDT increased the number of oocytes retrieved (19.0 [14.0, 25.0] vs. 16.0 [12.0, 21.0], p < 0.001) and blastocysts (3.0 [2.0, 6.0] vs. 3.0 [2.0, 5.0], p = 0.001), but not euploid blastocysts (2.0 [1.0, 3.0] vs. 1.0 [1.0, 3.0], p = 0.111), compared with the hCG trigger after PSM. Limitations, reasons for caution This was a single-center retrospective cohort study. The baseline characteristics of SDT and LDT differed from those of the hCG group because of clinical decision preferences. PSM was used to control for these effects and generate a balanced cohort. Pregnancy outcomes after embryo transfer has not been assessed yet. Wider implications of the findings The hormone change curve induced by LDT is more similar to the natural cycle. Probably LDT could also benefit poor to normal ovarian responders in IVF/ICSI cycles. And LDT might help in fresh embryo transfer cycles because of its advantage on endometrial receptivity. Trial registration number the National Natural Science Foundation of China (Grant No.82171626)

Intrahepatic cholestasis of pregnancy after ovarian hyperstimulation syndrome with wild-type ABCB4 gene: a peculiar case and literature review

BackgroundIntrahepatic cholestasis of pregnancy (ICP) in the first trimester occurring after ovarian hyperstimulation syndrome (OHSS) is a rare condition and few cases are reported in the literature. Hyperestrogenism may explain this problem in genetically predisposed women. The objective of this article is to report one of these rare cases and offer an overview of the other published cases.Case presentationWe report a case of severe OHSS followed by ICP in the first trimester. The patient was admitted to the intensive care unit and was treated according to the guidelines for the management of OHSS. Moreover, the patient also received ursodeoxycholic acid for ICP, which brought to an improvement of her clinical conditions. The pregnancy continued without other complications until the 36th week of gestation, when the patient developed ICP in the third trimester and underwent cesarean section for increased bile acid levels and cardiotocographic (CTG) pathologic alterations. The newborn was a healthy baby weighing 2500 gr. We also reviewed other case reports published by other authors about this clinical condition. We present what is, to our knowledge, the first case of ICP developed in the first trimester of pregnancy after OHSS in which genetic polymorphisms of ABCB4 (MDR3) have been investigated.ConclusionsICP in the first trimester might be induced by elevated serum estrogen levels after OHSS in genetically predisposed women. In these women, it might be useful to check for genetic polymorphisms to know if they have a predisposition for ICP recurrence in the third trimester of pregnancy.

Chronic kidney disease, female infertility, and medically assisted reproduction: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology

Fertility is known to be impaired more frequently in patients with chronic kidney disease than in the general population. A significant proportion of chronic kidney disease patients may therefore need Medically Assisted Reproduction. The paucity of information about medically assisted reproduction for chronic kidney disease patients complicates counselling for both nephrologists and gynaecologists, specifically for patients with advanced chronic kidney disease and those on dialysis or with a transplanted kidney. It is in this context that the Project Group on Kidney and Pregnancy of the Italian Society of Nephrology has drawn up these best practice guidelines, merging a literature review, nephrology expertise and the experience of obstetricians and gynaecologists involved in medically assisted reproduction. Although all medically assisted reproduction techniques can be used for chronic kidney disease patients, caution is warranted. Inducing a twin pregnancy should be avoided; the risk of bleeding, thrombosis and infection should be considered, especially in some categories of patients. In most cases, controlled ovarian stimulation is needed to obtain an adequate number of oocytes for medically assisted reproduction. Women with chronic kidney disease are at high risk of kidney damage in case of severe ovarian hyperstimulation syndrome, and great caution should be exercised so that it is avoided. The higher risks associated with the hypertensive disorders of pregnancy, and the consequent risk of chronic kidney disease progression, should likewise be considered if egg donation is chosen. Oocyte cryopreservation should be considered for patients with autoimmune diseases who need cytotoxic treatment. In summary, medically assisted reproduction is an option for chronic kidney disease patients, but the study group strongly advises extensive personalised counselling with a multidisciplinary healthcare team and close monitoring during the chosen medically assisted reproduction procedure and throughout the subsequent pregnancy.Graphical abstract