Age at menarche and risk of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI cycles: a retrospective cohort study.

OBJECTIVES: We aimed to explore the association between age at menarche (AAM) and ovarian hyperstimulation syndrome (OHSS) in fresh in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: A retrospective cohort study. SETTING: Data were collected from a large obstetrics and gynaecology hospital in Sichuan, China. PARTICIPANTS: This study included 17 419 eligible women aged ≤40 years who underwent the first IVF/ICSI cycles from January 2015 to December 2021. Women were divided into three groups according to their AAM: ≤12 years (n=5781), 13-14 years (n=9469) and ≥15 years (n=2169). RESULTS: The means of age at recruitment and AAM were 30.4 years and 13.1 years, respectively. Restricted cubic spline models suggested that early menarche age increased the risk of OHSS. The multivariable logistic analysis showed that women with menarche age ≤12 years were more likely to suffer from OHSS (OR 1.321, 95% CI 1.113 to 1.567) compared with those aged 13-14 years among the whole cohort. This significant relationship remained in women administered with different ovarian stimulation protocols and gonadotrophin doses. When stratified by female age, this correlation was presented only in patients aged ≤30 years (OR 1.362, 95% CI 1.094 to 1.694). And the mediation analysis showed that the relationship between AAM and OHSS was totally mediated by antral follicle counts (AFC). CONCLUSION: Menarche age earlier than 12 years may increase the OHSS risk in women aged ≤30 years through the mediation of AFC. More prospective studies are required to verify the results.

Nonlinear relationship between gonadotropin total dose applied and live birth rates in non-PCOS patients: a retrospective cohort study.

The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI [1.05, 2.28]); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI [0.89, 0.99]) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction < 0.05).

Serum erythropoietin level is increased during stimulation for IVF but not in OHSS.

BACKGROUND: Erythropoietin (Epo) is a potent vascular growth factor that induces angiogenesis and antiapoptotic signalling. We investigated whether the development of numerous follicles and corpora lutea during in vitro fertilization (IVF) cycle affects circulating Epo levels and further, if Epo could be used as a novel marker for ovarian hyperstimulation syndrome (OHSS). METHODS: 24 women were included in the uncomplicated IVF group and 35 women in the OHSS group. Repeated blood samples from both groups were analysed for Epo, progesterone, blood haemoglobin, and creatinine. Follicular fluid from the IVF group was analysed for Epo and progesterone. Repeated measure analysis was performed for the variables and circulating Epo levels were compared between the IVF group and early OHSS. Furthermore, related growth factors, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) were analysed from subgroup of women to test for correlation with Epo. RESULTS: During IVF, circulating Epo increased from natural mid-luteal phase to stimulated mid-luteal phase (median 9.5; 95% CI 7.2-13.4 IU/L and 12.5; 10.3-13.4 IU/L; p = 0.003). In cycles resulting in pregnancy, Epo level decreased 14 days after oocyte pick-up (OPU) and remained low thereafter. In cycles not resulting in pregnancy, Epo level increased again 35 days after OPU. Follicle fluid Epo concentration was 1.5 times higher than the serum concentration (median 15.4; 95% CI 10.4-19.2 IU/L vs. 10.2; 8.8-12.7; p = 0.006). There was no difference in circulating Epo concentration between early OHSS and uncomplicated IVF. Circulating Epo did not correlate with VEGF or HIF-1. CONCLUSIONS: Circulating Epo levels fluctuate during IVF cycle. We hypothesise this may suggest Epo's involvement in ovarian physiology and angiogenesis. However, Epo was not a clinical marker for OHSS.

Is controlled ovarian stimulation safe in patients with hormone receptor-positive breast cancer receiving neoadjuvant chemotherapy?

INTRODUCTION: Controlled ovarian stimulation (COS) for oocyte/embryo cryopreservation is the method of choice for fertility preservation (FP) in young patients diagnosed with early-stage breast cancer (eBC). Nevertheless, some challenges still question its role, particularly in the neoadjuvant setting, where concerns arise about potential delay in the onset of anticancer treatment, and in hormone receptor-positive (HR+) disease, as cancer cells may proliferate under the estrogenic peak associated with stimulation. Therefore, this review aims to examine the available evidence on the safety of COS in eBC patients eligible for neoadjuvant treatment (NAT), particularly in HR+ disease. METHODS: A comprehensive literature search was conducted to identify studies evaluating the feasibility and safety of COS in eBC and including patients referred to NAT and/or with HR+ disease. Time to NAT and survival outcomes were assessed. RESULTS: Of the three matched cohort studies assessing the impact of COS on time to start NAT, only one reported a significant small delay in the cohort undergoing COS compared with the control group, whereas the other studies found no difference. Regarding survival outcomes, overall, no increased risk of recurrence or death was found, either in patients undergoing COS in the neoadjuvant setting regardless of HR expression or in HR+ disease regardless of the timing of COS relative to surgery. However, there are no data on the safety of COS in the specific combined scenario of HR+ disease undergoing NAT. CONCLUSION: Neither the indication to NAT nor the HR positivity constitutes per se an a priori contraindication to COS. Shared decision making between clinicians and patients is essential to carefully weigh the risks and benefits in each individual case. Prospective studies designed to specifically investigate this issue are warranted.

Sublingual human chorionic gonadotropin as an adjuvant to ovulation induction.

OBJECTIVE: To evaluate the efficacy of sublingually administered human chorionic gonadotropin (HCG) in combination with clomiphene citrate (CC) or letrozole (LTZ) for ovulation induction. METHODS: In this prospective, double-blind, randomized study, the patients were divided into two placebo groups and two intervention groups using CC, LTZ, and HCG. RESULTS: There were no statistically significant differences in ovulation induction between the groups. We compared endometrial thickness at the beginning of the cycle and during the pre-ovulatory period, and detected a moderately positive correlation when CC was administered with HCG. CONCLUSIONS: Sublingual HCG with CC caused a moderately positive correlation with endometrial thickening when compared with that at the beginning of the cycle and during the pre-ovulatory period. There was no significant change in the number of pre-ovulatory follicles.

Personalizing the first dose of FSH for IVF/ICSI patients through machine learning: a non-inferiority study protocol for a multi-center randomized controlled trial.

BACKGROUND: Adequately selecting the initial follicle-stimulating hormone (FSH) dose during controlled ovarian stimulation (COS) is key for success in assisted reproduction. The objective of COS is to obtain an optimal number of oocytes to increase the chances of achieving a pregnancy, while avoiding complications for the patient. Current clinical protocols do achieve good results for the majority of patients, but further refinements in individualized FSH dosing may reduce the risk of poor ovarian response while also limiting the risk of ovarian hyperstimulation syndrome (OHSS) risk. Models to select the first FSH dose in COS have been presented in literature with promising results. However, most have only been developed and tested in normo-ovulatory women under the age of 40 years. METHODS: This is a randomized, controlled, multicenter, single blinded, clinical trial. This study will be performed in 236 first cycle in vitro fertilization (IVF) and/or ICSI (intracytoplasmic sperm injection) patients, randomized 1:1 in two arms. In the intervention arm, the dose of FSH will be assigned by a machine learning (ML) model called IDoser, while in the control arm, the dose will be determined by the clinician following standard practice. Stratified block randomization will be carried out depending on the patient being classified as expected low responder, high responder, or normo-responder. Patients will complete their participation in the trial once the first embryo transfer result is known. The primary outcome of the study is the number of metaphase II (MII) oocytes retrieved at ovarian pick up (OPU) and the hypothesis of non-inferiority of the intervention arm compared to the control. Secondary outcomes include the number of cycle cancelations (due to low response or no retrieval of mature oocytes), risk of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancy and live birth rates per first transfer. DISCUSSION: To our knowledge, this is the first randomized trial to test clinical performance of an all-patient inclusive model to select the first dose of FSH for COS. Prospective trials for machine learning (ML) models in healthcare are scarce but necessary for clinical application. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05948293 . Registered on 14 July 2023.

First case report of serous otitis media as a complication of severe ovarian hyperstimulation syndrome: Case report and literature review.

Ovarian hyperstimulation syndrome (OHSS) may be a severe complication of controlled ovarian hyperstimulation during assisted reproductive technology. During OHSS, fluid shifts from the intravascular space to the third-space compartments as the result of an increase in capillary permeability. This can cause fluid accumulation in peritoneal as well as thoracic cavities. The patient presented with symptoms of severe OHSS (bilateral hydrothorax and pulmonary effusion), requiring bilateral ultrasound-guided paracentesis and bilateral thoracentesis during her Emergency Room visits and hospitalization. Due to distant effects from the increased capillary permeability, the patient presented fluid in the middle ear, which led to the development of serous otitis media 12 days after egg retrieval. This was resolved 2-3 weeks later after being treated with antihistamines and antibiotics given by her Ear, Nose, and Throat doctor. OHSS risk may be reduced by continuous monitoring of patients undergoing ovulation induction, using an appropriate gonadotropin dosage, and using additional agents known to decrease its risk. If OHSS still occurs, symptomatic treatment and a multidisciplinary team of professionals may be needed to prevent fluid build-up complications. In contrast to many published articles about OHSS and its complications, this is the first case report of a patient presenting serous otitis media as a complication of severe OHSS.

Assisted Reproductive Technology in the Presence of Polycystic Ovary Syndrome: Current Evidence and Knowledge Gaps.

OBJECTIVE: In this narrative review, we discuss the current evidence as well as the knowledge gaps concerning assisted reproductive technology (ART) indications, protocols, and results in the presence of polycystic ovary syndrome (PCOS). METHODS: An electronic literature search was performed for English-language publications in the last decade in databases such as PubMed, Medline, the Web of Sciences, Embase, and Scopus. RESULTS: We found evidence that ovarian steroidogenesis and folliculogenesis are deeply altered by PCOS; however, the oocyte quality and pregnancy rates after ART are not affected. Patients with PCOS are more sensitive to the action of exogenous gonadotropins and more likely to develop ovarian hyperstimulation syndrome. This risk can be mitigated by the adoption of the gonadotropin-releasing hormone antagonist protocols for pituitary blockade and ovarian stimulation, along with frozen embryo transfer, without compromising the odds of achieving a live birth. Pregnancy complications, such as miscarriage, gestational diabetes, preeclampsia, and very preterm birth, are more frequent in the presence of PCOS, requiring more intense prenatal care. It remains uncertain whether weight reduction or insulin sensitizers used before ART are beneficial for the treatment outcomes. CONCLUSION: Although PCOS is not a drawback for ART treatments, the patients need special care to avoid complications. More in-depth studies are needed to uncover the mechanisms of follicular growth, gamete maturation, and endometrial differentiation during ART procedures in the presence of PCOS.

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 in 2016.

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.

Fertility preservation in patients with gynaecologic malignancy: Response to ovarian stimulation and long-term outcomes.

OBJECTIVE: To the best of our knowledge, the available evidence on the effect and efficacy of controlled ovarian stimulation (COS) in this group of patients remains poorly reported. Concerns related to the impact of stimulation to cancer progression and recurrence, as well as the risk of disease dissemination during egg collection, might explain the aforementioned trend. METHODS: Overall, our FP Service received 192 gynaecological referrals, between 2005 and 2021, regarding gynaecologic conditions mainly cancer related. A total of 68 (35.4%) patients underwent COS. These patients were diagnosed with the following gynaecologic pathologies: 33 cases (48,5%) of cervical cancer were noted (stage 1b1-2b), 25 ovarian pathology (36.7%), 9 cases (13.2%) of endometrial cancer, and a single case of vaginal cancer (1.5%). RESULTS: The mean age of patients attending the fertility preservation service was 31.5 (std 5.8). The patients presenting to their initial appointment with a mean BMI 24.5 (IQR 6.9) and a median AFC of 12 (IQR 13). The mean duration of COS was 11 days (IQR 3), and the median dose of gonadotrophins was calculated at 300 IU (IQR 75 IU). In 95.4% of the cases, GnRH agonist was used as a trigger for final maturation. The median number of follicles measuring more than 14 mm at the time of trigger was 11 (IQR 8), whereas the median number of oocytes collected was 11 (IQR 9). The complication rate was reported at less than 2%. So far, one in four women of this FP group (17/68, 25% of the overall group) returned to our service to claim their cryopreserved eggs/embryos and successful livebirths were reported in 58.8% of this sample (10/17 cases). The mean time to return to use their oocytes/embryos was 36 months (min value 16 months - max value 85 months). There was no significant difference in mortality rate between patients who received FP vs those who did not (hazard ratio of mortality was estimated at 0.91 (p-value 0.88)). CONCLUSION: Based on our findings, ovarian stimulation for patients presenting with gynaecologic malignancy is a safe and efficient method of fertility preservation. Undoubtedly, the sample size is limited, however our results are reassuring and highlight the efficacy of COS for the purpose of FP based on data coming from the largest Assisted Conception Unit of the South-East of the UK.

Race, ovarian responsiveness, and live birth after in vitro fertilization.

OBJECTIVE: To determine if ovarian responsiveness to gonadotropin stimulation differs by race/ethnicity and whether this predicts live birth rates (LBRs) in non-White patients undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Academic infertility center. PATIENT(S): White, Asian, Black, and Hispanic patients undergoing ovarian stimulation for IVF. INTERVENTION(S): Self-reported race and ethnicity. MAIN OUTCOME MEASURE(S): The primary outcome was ovarian sensitivity index (OSI), defined as (the number of oocytes retrieved ÷ total gonadotropin dose) × 1,000 as a measure of ovarian responsiveness, adjusting for age, body mass index, infertility diagnosis, and cycle number. Secondary outcomes included live birth and clinical pregnancy after first retrievals, adjusting for age, infertility diagnosis, and history of fibroids, as well as miscarriage rate per clinical pregnancy, adjusting for age, body mass index, infertility diagnosis, duration of infertility, history of fibroids, and use of preimplantation genetic testing for aneuploidy. RESULT(S): The primary analysis of OSI included 3,360 (70.2%) retrievals from White patients, 704 (14.7%) retrievals from Asian patients, 553 (11.6%) retrievals from Black patients, and 168 (3.5%) retrievals from Hispanic patients. Black and Hispanic patients had higher OSIs than White patients after accounting for those with multiple retrievals and adjusting for confounders (6.08 in Black and 6.27 in Hispanic, compared with 5.25 in White). There was no difference in OSI between Asian and White patients. The pregnancy outcomes analyses included 2,299 retrievals. Despite greater ovarian responsiveness, Black and Hispanic patients had lower LBRs compared with White patients, although these differences were not statistically significant after adjusting for confounders (adjusted odds ratio, 0.83; 95% confidence interval [CI], 0.63-1.09, for Black; adjusted odds ratio, 0.93; 95% CI, 0.61-1.43, for Hispanic). Ovarian sensitivity index was modestly predictive of live birth in White and Asian patients but not in Black (area under the curve, 0.51; 95% CI, 0.38-0.64) and Hispanic (area under the curve, 0.50; 95% CI, 0.37-0.63) patients. CONCLUSION(S): Black and Hispanic patients have higher ovarian responsiveness to stimulation during IVF but do not experience a consequent increase in LBR. Factors beyond differences in responsiveness to ovarian stimulation need to be explored to address the racial/ethnic disparity established in prior literature.

Early pregnancy complications including recurrent pregnancy loss and obesity.

This review on early pregnancy complications and obesity will focus on the known pregnancy complications such as miscarriage (whether spontaneous or after fertility treatment), polycystic ovaries and risk of miscarriage, recurrent pregnancy loss, ectopic pregnancy, hyperemesis gravidarum and birth defects. Evidence will be assessed and mechanistic pathways for the outcomes will be described. We know that obesity is now a pandemic and has an impact on early pregnancy complications. The evidence has been summarised to provide the reader with a comprehensive overview and advice for pregnant women with obesity in early pregnancy.

Elevated antimüllerian hormone levels are not associated with preterm delivery after in vitro fertilization or ovulation induction.

OBJECTIVE: To investigate the association between antimüllerian hormone (AMH) and preterm birth risk in a larger cohort of patients who underwent either in vitro fertilization or ovulation induction with intrauterine insemination at a US academic fertility center. DESIGN: Retrospective cohort study. SETTING: Single academic fertility center. PATIENT(S): Live singleton births from patients who underwent in vitro fertilization or ovulation induction between 2016 and 2020 at a single academic fertility center were included in this study. Patients were excluded if they had a missing prepregnancy AMH level, a pregnancy using donor oocytes or a gestational carrier, multiple gestations, a delivery before 20 weeks gestation, or a cerclage in place. INTERVENTION(S): AMH level. MAIN OUTCOME MEASURE(S): The primary outcome was the proportion of preterm delivery. Secondary outcomes included the rate of pregnancy-induced hypertension, gestational diabetes, and small for gestational age. RESULT(S): In the entire cohort (n = 875), 8.4% of deliveries were preterm. The mean AMH values were similar between those with term and preterm births (3.9 vs. 4.2 ng/mL). Similar proportions of patients with term and preterm deliveries had AMH levels greater than the 75th percentile (25% vs. 21%). The odds of preterm birth were similar by AMH quartile after adjusting for the history of preterm birth. Similarly, in the polycystic ovary syndrome (PCOS) cohort, there was no difference between mean AMH values of term and preterm births (n = 139, 9.6 vs. 10.0 ng/mL). The proportions of patients with PCOS with AMH levels greater than the 75th percentile were similar between those with term and preterm deliveries (25% vs. 22%). The odds of preterm birth were similar by the AMH quartile after adjusting for the history of preterm birth. CONCLUSION(S): Elevated AMH levels were not associated with an increased risk of preterm birth in patients who conceived after in vitro fertilization and ovulation induction, including patients with PCOS. Although studies suggest that AMH levels may help stratify the risk of preterm birth in this population, our findings indicate that further studies are needed before clinical application.

A case report of Ovarian hyperstimulation syndrome and corpus luteum rupture in twin pregnancies with IVF-ET.

INTRODUCTION: Ovarian hyperstimulation syndrome (OHSS) is a common complication during assisted conception treatment, mostly seen in patients with ovarian hyperresponsiveness such as polycystic ovary syndrome, especially in post-invitro fertilization and embryo transfer (IVF-ET) pregnancies. Its main symptoms are abdominal distension, abdominal pain, nausea and vomiting with ascites, pleural fluid, leukocytosis, hemoconcentration and hypercoagulation. This disease is a self-limiting disease and can be gradually cured by rehydration, albumin infusion and correction of electrolyte disorders in moderate to severe cases. Luteal rupture is a more common gynecological emergency abdomen. The combination of twin pregnancy, OHSS and ruptured corpus luteum is very rare. We successfully avoided the stimulation of the risk of pregnancy abortion by surgical exploration through dynamic ultrasound monitoring and vital signs observation in the absence of experience in primary care, and the patient hard-won twin pregnancy was successfully treated conservatively. PATIENT CONCERNS: The patient is a 30-year-old post-IVF-ET woman with an established twin pregnancy, OHSS and sudden onset of lower abdominal pain. DIAGNOSIS: Twin pregnancy, OHSS combined with ruptured corpus luteum. INTERVENTIONS: Rehydration, albumin infusion, low molecular heparin for thromboprophylaxis, luteinizing support, ambulatory ultrasound monitoring. OUTCOMES: After more than 10 days of standardized treatment for OHSS, dynamic ultrasound monitoring and close observation of vital signs, the patient was discharged cured of her condition and is continuing her pregnancy. CONCLUSION: Our case shows that the possibility of acute abdominal rupture of the corpus luteum is still present in the case of combined OHSS in pregnancy, and that some patients with corpus luteum rupture can heal spontaneously during close testing to avoid the increased risk of miscarriage with surgical exploration.

Long-acting gonadotropin-releasing hormone agonist trigger in fertility preservation cycles before chemotherapy.

BACKGROUND: Oocytes/embryo cryopreservation and ovarian function suppression with gonadotropin-releasing hormone (GnRH) agonists (GnRHas) are two established strategies for preserving fertility in patients with cancer, frequently both being offered to the same woman. As the first injection of GnRHa should be administered before chemotherapy, it is usually performed in the luteal phase of the urgent controlled ovarian stimulation (COS) cycle. The GnRHa flare-up effect on recently stimulated ovaries may cause ovarian hyperstimulation syndrome (OHSS) and this risk may discourage some oncologists to offer an ovarian function preservation method with proven efficacy. We suggest the long-acting GnRHa as an option to trigger ovulation for egg retrieval in oncological patients, whenever ovarian suppression during chemotherapy is planned. PATIENTS AND METHODS: We retrospectively analyzed prospectively collected data from all consecutive ovarian stimulation cases in oncological patients for oocyte cryopreservation from 2016 to 2021 in a single academic referral center. The COS was performed according to good clinical practice standards. Since 2020 long-acting GnRHa trigger was offered to all patients for whom ovarian suppression after cryopreservation was planned. All other patients served as controls, stratified for the triggering method used: highly purified chorionic gonadotrophin 10 000 UI or short-acting GnRHa 0.2 mg. RESULTS: Mature oocytes were collected, with the expected maturation rate, in all the 22 cycles triggered with GnRHa. The mean number of cryopreserved oocytes was 11.1 ± 4, with a maturation rate of 80% (57%-100%), versus 8.8 ± 5.8, 74% (33%-100%) with highly purified chorionic gonadotrophin and 14 ± 8.4, 80% (44%-100%) with short-acting GnRHa. No case of OHSS was observed after long-acting GnRHa triggering and by 5 days after egg retrieval most patients had reached luteinizing hormone levels showing suppression. CONCLUSIONS: Our preliminary data show that long-acting GnRHa is efficacious in inducing the final oocytes' maturation, reducing OHSS risk and suppressing ovarian function by the start of chemotherapy.

Incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders after gonadotropin-releasing hormone (GnRH) agonist trigger in "freeze-all" approach.

OBJECTIVE: To determine the incidence and severity of ovarian hyperstimulation syndrome (OHSS) in high responders (25-35 follicles with a diameter of ≥12 mm on day of triggering) who received a gonadotropin-releasing hormone (GnRH) agonist to trigger final follicular maturation. METHODS: We used individual data from women who participated in four different clinical trials and were high responders to ovarian stimulation in a GnRH antagonist protocol in this retrospective combined analysis. All women were evaluated for signs and symptoms of OHSS using identical criteria based on Golan's system (1989). RESULTS: High responders (n = 77) were of different ethnicities. There were no differences in baseline characteristics between women with or without signs and symptoms of OHSS. Mean ± standard deviation baseline data were: age, 32.3 ± 3.5 years; anti-Müllerian hormone, 42.4 ± 20.7 pmol/L; antral follicle count, 21.5 ± 9.2. Before triggering, duration of stimulation was 9.5 ± 1.6 days and the mean number of follicles with a diameter of ≥12 mm and ≥17 mm was 26.5 ± 4.4 and 8.8 ± 4.7, respectively. Mean serum estradiol (17,159 pmol/l) and progesterone (5.1 nmol/l) levels were high at 36 h after triggering. Overall, 17/77 high responders (22%) developed signs and symptoms of mild OHSS which lasted 6-21 days. The most frequently prescribed medication was cabergoline to prevent worsening of OHSS. No severe OHSS occurred and no OHSS cases were reported as serious adverse events. CONCLUSIONS: High responders receiving GnRH agonist for triggering should be informed that they may experience signs and symptoms of mild OHSS.

In praise of ovulation induction for the management of anovulatory subfertility.

Rapid advances in assisted reproductive technology have revolutionized fertility treatments for couples worldwide seeking a pregnancy. Although this is promising, concerns are emerging over the overuse of unnecessary assisted conception treatments, particularly among couples with anovulatory subfertility. Some experts are calling for the cessation of ovulation induction as the primary treatment of anovulatory subfertility in favour of more sophisticated assisted conception treatments. In the absence of other causes of subfertility, ovulation induction in patients with type 1 and type 2 anovulation disorders can achieve an up to 80% ovulation rate with a 40% cumulative pregnancy rate and few adverse effects. Considering the various risks and high costs associated with assisted reproductive technology treatments, it is hard to argue for their cost-effectiveness when simpler, safer and cheaper pharmacological ovulation induction could achieve comparable pregnancy rates. We argue here for the safe, effective and ethical use of ovulation induction in this population, supplemented by a judicious use of assisted conception treatments. We emphasize the essential role of ovulation induction as a first-line intervention for couples with anovulatory subfertility delivered within a patient-centred multidisciplinary care model and with a clear escalation pathway to use assisted reproductive technology treatments based on the person's response, characteristics and treatment preference.

Factors associated with spontaneous miscarriage risk in IUI treatment: A retrospectively cohort of 31,933 cycles.

To determine the factors associated with intrauterine insemination (IUI) miscarriages and reduce the IUI miscarriage rate, a retrospective study was performed by reviewing 31,933 IUI cycles from 2006 to 2018. The overall there were 14.50% clinical pregnancies, and 16.74% miscarriages. Logistic regression revealed the following three predictive variables: females aged ≥ 35 years (odds ratio [OR] = 2.131; p < 0.001), spontaneous miscarriage history (OR = 1.513; p = 0.005), and ovarian stimulation schemes such as clomiphene citrate (CC) (OR = 1.459; p = 0.003). The natural cycle led to a lower miscarriage rate for patients without spontaneous miscarriage history both for those over 35 years old (OR = 0.402; p = 0.034) and for those under 35 years old (OR = 0.806; p = 0.017). Gonadotropin (Gn) showed the lowest miscarriage rate for patients without abortion history, though no significant differences were found. Patients under 35 with a history of miscarriage were protected from miscarriage by using CC and Gn together (OR = 0.516; p = 0.032). No significant differences were found between various ovarian protocols when patients with abortion history were aged ≥ 35 years (p = 0.606). CC + Gn showed the lowest miscarriage rate. In conclusion, the natural cycle could be suggested for infertility couples to minimize abortion risk. When ovarian induction is required, CC + Gn had the lowest miscarriage rate for women with a history of spontaneous miscarriage while Gn is more successful for individuals without such a history.

Effect of increased gonadotropin dosing on maternal and neonatal outcomes in predicted poor responders undergoing IVF: follow-up of a randomized trial.

OBJECTIVE: To evaluate, in women scheduled for IVF with predicted poor ovarian response, the effect of increased dosing of gonadotropin on maternal and neonatal outcomes compared with standard dosing. STUDY DESIGN: We performed a follow-up study of an open-labelled randomized controlled trial comparing increased (225 or 300 IU/d) versus standard (150 IU/d) dose gonadotrophins on cumulative live birth rates. We randomized 661 women with a predicted poor ovarian response (based on their antral follicle count) scheduled for their first IVF/ICSI cycle. Here, we report on maternal and neonatal outcomes between increased and standard dosing groups. RESULTS: There was a trend of increased risk of gestational diabetes mellitus in the increased gonadotrophin dose group compared with the standard group in both cumulative live birth pregnancies (14.8% vs. 7.8%, relative risk (RR) 1.90, 95% confidence interval (CI) 0.96-3.74, P = 0.06) and live birth pregnancies in the first transfer (15.2% vs. 7.7%, RR 1.98, 95 %CI 0.93-4.19, P = 0.08), without reaching statistical significance. The occurrence of gestational diabetes mellitus was significantly higher in the increased gonadotrophin dose group (24/149, 16.1% vs. 8/128, 6.3%; risk ratio (RR) 2.58, 95 %CI 1.19 to 5.54, P = 0.02) in singleton pregnancies. In women with first embryo transfer cycle, maternal hypothyroidism occurred also more frequent in the increased gonadotrophin dose group than the standard group (16.0% vs. 6.8%, RR 2.34, 95 %CI:1.07-5.11, P = 0.03). CONCLUSIONS: In women with predicted poor ovarian response, increased dosing of gonadotropin may result in an increased risk of gestational diabetes mellitus and maternal hypothyroidism.