Genuine Empty Follicle Syndrome Research Articles

Prevalence of FSH-R Asn680Ser and Ala307Thr receptor polymorphism and their correlation with ART outcomes among infertile Indian-Asian women-a prospective cohort study.

The present prospective cohort study evaluated the prevalence of FSH-R receptor Asn680Ser and Ala307Thr among infertile Indian women and the correlation of these polymorphisms with ART outcomes. Total 804 infertile and 209 fertile controls were enrolled for FSH-R analysis. Correlation of different genotypes with ovarian reserve markers, IVF parameters, and cumulative live birth rates (CLBR) was done among women undergoing IVF. In fertile controls, at 680 position GG (Ser/Ser) was the most common genotype; but among infertile women, all the genotypes were equally distributed. There was no significant difference in ovarian response parameters, oocyte yield, and CLBR among the three genotype groups. Empty follicle syndrome (EFS) was highest in women with AA or AG type at both positions. On categorisation of unexpected poor responders according to POSEIDON stratification; GG genotype at both positions had the lowest risk ratio of low-oocyte yield in ART cycles, but these differences were not statistically significant. This is the largest study from Indian ethnicity showing GG (Ser/Ser) genotype is most common among fertile women. The effect of FSH-R genotypes is very marginal on IVF parameters and is not reflected in CLBR. More prospective data may be required on the correlation of these genotypes with genuine EFS, thus stratifying the next cycles with self or donor oocytes. Routine genetic testing of FSH-R polymorphism should not be done except in a research setting. As both 680 and 307 positions are in linkage disequilibrium, only 680 position analysis may be done in a research setting.

Exome sequencing in genuine empty follicle syndrome: Novel candidate genes

Objective(s)Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved in an IVF cycle despite apparently normal follicular development and meticulous follicular aspiration following ovulation induction. The EFS is called genuine (gEFS) when the trigger administration is correct. The existence of gEFS is a subject of controversy, and it is quite rare with an undetermined etiology. Genetic defects in specific genes have been demonstrated to be responsible for this condition in some patients. Our objective was to identify novel genetic variants associated with gEFS. Study DesignWe conducted a prospective observational study including 1,689 egg donors from July 2017 to February 2023. WES were performed in patients suffering gEFS. ResultsOnly 7 patients (0.41 %) exhibited gEFS after two ovarian stimulation cycles and we subsequently performed whole exome sequencing (WES) on these patients. Following stringent filtering, we identified 6 variants in 5 affected patients as pathogenic in new candidate genes which have not been previously associated with gEFS before, but which are involved in important biological processes related to folliculogenesis. These genetic variants included c.603_618del in HMMR, c.1025_1028del in LMNB1, c.1091-1G > A in TDG, c.607C > T in HABP2, c.100 + 2 T > C in HAPLN1 and c.3592_3593del in JAG2. ConclusionAs a conclusion, we identified new candidate genes related to gEFS that expand the mutational spectrum of genes related to gEFS.This study show that WES might be an efficient tool to identify the genetic etiology of gEFS and provide further understanding of the pathogenic mechanism of gEFS.

Validation of the existence of genuine Empty follicle syndrome, versus false empty follicle syndrome to make definitive decisions in cases where recurrent IVF failure encountered secondary to absence of oocytes on ovum pick up-a short communication

Aim: Worldwide a big altercation exists with regards to the actual existence of the term “ Empty follicle syndrome’’(EFS), so much so that certain big authorities in the field have been believing that true EFS does not exist. Basically EFS is a syndrome when no functionally intact oocyte get retrieved when attempting an oocyte pick up (OPU) for a successful in vitro fertilization (IVF), however such patients encounter recurrent IVF failures. Since it is has become a big problem for the treating reproductive endocrinologist, besides the patient encountering recurrent IVF failures, it has become essential to differentiate the true EFS alias genuine Empty follicle syndrome (gEFS) from what is labeled today as the false empty follicle syndrome (fEFS). In view of the recently documented presence of mutations, gEFS got verified and appears to silence this biggest conflict that arose secondary to the existence of a false empty follicle syndrome(fEFS), where one could manage to get successful IVF outcomes subsequent to repeated hCG injections/ gonadotropin releasing hormone (GnRH) agonist in addition to pregnancy, with lot of clinicians believing there is no true term like EFS. Methods: Recently Yang et al., performed a study In tertiary a university based reproductive center in China that was comprised of a big cohort of patients that presented with gEFS. Genetic evaluation was conducted on 35 non correlated infertile patients who went through 16 failed IVF cycles in addition to oocyte degeneration, besides the subjects got a diagnosis of possessing a particular kind of EFS- cumulus oocytes complexes (COC’s) but possessed oocytes that were undergoing degeneration, with the utilization of whole –exome sequencing along with targeted Sanger sequencing. Results: Yang et al., found 22 innovative genetic variant of zona pellucida (ZP), genes in 18 subjects, that were inclusive of 20 variants in ZP 1 gene, 2 in ZP 2 gene in addition to 1 recurring variant in ZP3 gene that had been earlier documented. The homogenous /compound heterogenous ZP 1 mutations were inherited in an autosomal recessive manner, while the heterogenous variants of ZP 2 as well as ZP3 genes possessed an autosomal dominant manner of inheritance. Conclusions: These mutations were anticipated to be harmful in silico along with got further experimentally corroborated to be functionally null dependent on their ectopic expression in vitro. Thus with this further evidence that has been recently provided with regards to the existence of genuine Empty follicle syndrome (gEFS), it is significant for the youngsters to realize if they encounter similar cases after trial of rescue hCG injections / GnRH) agonist, not to further keep waiting, but evaluate further with regards to the existence of mutations for Zona Pellucida (ZP), ZP 1, ZP2 as well as ZP3 genes mutations, or LH/ chorionic gonadotropins receptor (LHCGR) gene mutation without subjecting the patient to repeated IVF, with her psychological as well as financial health in mind

Prevalence of Empty Follicle Syndrome in King Chulalongkorn Memorial Hospital

Objective: To investigate the prevalence of empty follicle syndrome (EFS), a condition in which no oocytes were retrieved after ovarian stimulation, categorized into genuine EFS (g-EFS) and false EFS (f-EFS), at the King Chulalongkorn Memorial Hospital (KCMH), Thailand. Materials and Methods: A retrospective study was conducted at the infertility clinic of the KCMH. Medical records of the assisted reproductive technology (ART) patients between January 2001 and October 2019 (5,523 patients) were reviewed. Exclusion criteria were the cases where ovulation occurred before oocyte retrieval or the cases with less than four follicles larger than 14 mm diameter on the day of triggering ovulation to minimize the absence of oocyte from the poor response. The patients with EFS, g-EFS, which are EFS with detectable urinary human chorionic gonadotropin (hCG), and f-EFS, which are EFS with undetectable urinary hCG, were identified. Prevalence of EFS was calculated. Results: There were three cases with EFS in the present study, which g-EFS was identified in one case and f-EFS in two cases. The prevalence of EFS was 0.054%, which g-EFS was 0.018% and f-EFS was 0.036%. Conclusion: EFS is a rare condition, particularly the g-EFS. Although EFS is rare, it causes tremendous stress and anxiety to both patients and physicians. Further study in the etiopathogenesis of EFS is required. Keywords: Empty follicle syndrome; Infertility; In vitro fertilization

Genuine Empty Follicle Syndrome: Role of Double Trigger and Delayed Oocyte Retrieval (DTDO).

Background:Empty follicle syndrome (EFS) is a condition of undetermined etiology where no oocytes are retrieved in an ART cycle despite adequate response to ovarian stimulation and diligent follicular aspiration. Because of the rarity of this condition, no much published strategies are available to tackle this.Aim:The aim of this study was to evaluate whether sequential administration of gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) as a trigger at 40 h and 36 h, respectively, before oocyte retrieval (OCR) could correct genuine empty follicle syndrome (GEFS).Study Setting and Design:This retrospective observational cohort study was conducted in a tertiary fertility center over a period of 6 years from January 2014 to December 2019. Patients with a history of GEFS were administered GnRHa and recombinant hCG subcutaneously at 40 h and 36 h, respectively, before OCR, i.e., double trigger and delayed oocyte retrieval (DTDO) (n = 13). The primary outcome measures studied were number of mature oocytes retrieved, oocyte maturation index (OMI), number of fertilized oocytes, and number of embryos available for embryo transfer. The secondary outcome measures were clinical pregnancy rate (CPR), miscarriage rate (MR) and live birth rate (LBR) per first frozen embryo transfer (FET) cycle, incidence of inadvertent premature ovulation, and ovarian hyperstimulation syndrome.Statistical Analysis:Comparison between the groups was analysed by Fisher's exact test and paired t-test.Results:Patients in the DTDO group showed a significant improvement (P < 0.01) in the number of mature oocytes retrieved, OMI, number of fertilized oocytes, and number of embryos available for embryo transfer. In the first FET cycle, CPR (44.44%), LBR (44.44%), and MR (11.11%) were observed in the DTDO group.Conclusion:Our findings implicate that double trigger and delayed OCR (DTDO) is a safe and efficacious treatment strategy for GEFS.

Severe ovarian hyperstimulation syndrome in a case of nonmutated recurrent genuine empty follicle syndrome

Empty follicle syndrome (EFS) is a rare event in which no oocytes are retrieved from apparently normal growing follicles with normal steroidogenesis despite meticulous follicular aspiration in assisted reproductive technology (ART) cycles. EFS is mainly of two types, genuine EFS and false EFS. Here, we report a case of a 24-year-old woman presenting with primary infertility with normal ovarian reserve and regular menstrual cycles, husband having severe “oligo-astheno-teratozoospermia,” and planned for ART treatment. We could not retrieve any oocytes in successive cycles despite optimum human chorionic gonadotropin (hCG) levels on the day of oocyte retrieval and using different management protocols mentioned until now in the literature. The whole genomic analysis was found to be normal (46, XX). Further, the patient had experienced severe ovarian hyperstimulation syndrome (OHSS) after the second cycle of ovarian stimulation despite no luteal hCG support. We were ineffectual to find the cause of recurrent EFS in this patient and therefore counseled the patient for donor oocytes. This case highlights the difficulty in treating genuine EFS patients and the need for monitoring serum estradiol levels during ovarian stimulation to prevent another serious complication of OHSS.

The critical role of ZP genes in female infertility characterized by empty follicle syndrome and oocyte degeneration

To identify the major causative gene(s) of genuine empty follicle syndrome (GEFS) characterized by oocyte degeneration. Genetic and functional studies. University-based reproductive medicine center. Thirty-five unrelated women with GEFS and oocyte degeneration. Whole-exome sequencing (WES) and targeted Sanger sequencing. Variants predicted by software and the functional effects of variants assessed via Western blot and immunofluorescence in Chinese hamster ovary (CHO) cells. We identified zona pellucida (ZP) gene variants in 18 individuals, which included 20 variants in the ZP1 gene, two variants in the ZP2 gene, and one previously reported recurrent variant in the ZP3 gene. The women carrying ZP variants constituted 51.43% of the GEFS cohort. The ZP1 variants were inherited in an autosomal recessive pattern; the ZP2 and ZP3 variants were inherited in an autosomal dominant pattern. All variants were predicted to be deleterious. Studies in CHO cells suggested that most ZP1 variants led to increased intracytoplasmic protein and some variants influenced the intracellular transportation of other ZP proteins. Variant p.R642Q of ZP2 caused the secretion of ZP2 protein with an increased molecular weight, suggesting altered protein modification. Variant p.I619N of ZP2 resulted in increased ZP2 protein in cell lysate and decreased ZP2 protein in culture medium. These results showed that ZP variants might block the intracellular transportation and secretion of ZP proteins and disrupt the zona pellucida. We identified novel variants of ZP genes in more than half the cohort with GEFS and oocyte degeneration. Variants of ZP genes caused protein intracellular sequestration and failure to assemble the ZP filaments, resulting in EFS and female infertility. Our findings not only reveal the critical roles of ZP genes but also pave the way for the efficient genetic diagnosis of females with GEFS and oocyte degeneration.

Does the empty follicle syndrome occur in cases of low number of maturing follicles in assisted reproduction?

The pathophysiology of the genuine empty follicle syndrome (EFS) is still debated. Ovarian aging has been contested as a cause of this condition. Our aim was to investigate the occurrence of the genuine EFS in cases of a low number of mature follicles in a prospective manner. Ninety-five infertile women were recruited and evaluated following conventional controlled ovarian stimulation (COS) with ≤ six follicles of ≥14 mm diameter on the day of hCG administration. Enrolled women were 37.5 ± 5.2 years of age with basal FSH level of 9.1 ± 3.7 mIU/L, antral follicle count (AFC) of 6.9 ± 4.6, and number of ≥14 mm follicles (on the day of hCG) of 3.4 ± 1.5. Among the 95 women, four were complicated by the genuine EFS (4.2%) with features of the depleted ovarian reserve. Comparison between these four cases and the 91 controls revealed significant differences between age, AFC, number of ≥14 mm follicles, and serum E2 level corresponding to 41.8 ± 1.7 versus 37.4 ± 5.2 years, 1.7 ± 0.6 versus 7.1 ± 4.5, 2.0 ± 0.8 versus 3.4 ± 1.5 follicles, and 356 ± 200 versus 975 ± 557 pg/mL, respectively. Post hoc analysis revealed that 56 among the 95 women fulfilled the Bologna criteria for poor ovarian response and all four cases matched the definition of the genuine EFS raising its incidence to 7.1% in this group. A logistic regression analysis showed that AFC was a significant factor in the development of the genuine EFS. We conclude that the genuine EFS complicates infertile women characterized by a low number of mature follicles. Our findings suggest that the mechanism behind this occurrence is associated with a more exhausted ovarian reserve.

Empty follicular syndrome: incidence in 2729 IVF cycles and prognosis in subsequent attempts

Introduction: The empty follicle syndrome (EFS) is described as the failure to retrieve oocytes at ovum pick-up (OPU) after an adequate controlled ovarian stimulation (COS) in patients undergoing in vitro fertilization (IVF). Objectives: To retrospectively calculate the incidence of EFS in IVF cycles and to assess the prognosis of these patients in subsequent IVF attempts. Patient(s): Women undergoing 2729 IVF cycles of homologous IVF at our IVF Unit in the years 2010-2014. Intervention(s): All cases with no retrieved oocytes at OPU were considered and divided into two sub-categories: (a) genuine EFS (gEFS), when a correct ovulation trigger was performed; and (b) false or iatrogenic EFS (iEFS), when no urinary hCG was detected the day of OPU, indicating a mistake in the administration of exogenous hCG for triggering. Main Outcome Measure(s): We calculated the incidence of EFS and then analyzed the outcome of subsequent IVF cycles in the same patients. Result(s): Eighty cases of EFS were identified in 2729 cycles (overall incidence 2.9%). Among EFS cases, 88% were gEFS and 11% were iEFS. The incidence of EFS was higher among patients above 40 years than in younger women (6.26% vs. 1.81%) (Table 1). Twenty-nine patients with gEFS underwent subsequent IVF cycles, and oocytes were retrieved in 88.6% of them, leading to a pregnancy rate/cycle of 20%, with no relevant differences according to age (PR/cycle 16.6% in younger women, 23.5% in women older than 40) (Table 1). Conclusion(s): We observed that EFS has an overall low prevalence among women undergoing IVF, but its incidence is five-times higher after 40 years of age, involving mainly patients with a low ovarian reserve. The iatrogenic form of EFS, iEFS, can be easily identified by testing hCG levels in urine samples the day of OPU, and occurs independently from age. Patients who experienced gEFS in an IVF attempt had a high chance of retrieving eggs in the subsequent IVF cycle and an acceptable pregnancy rate; interestingly, age did not negatively affect their prognosis.

Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low proportion of mature oocytes

Objective: Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation – 40 and 34 h prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved.Patients and methods: We compared the stimulation characteristics of 12 IVF cycles, which include the cycle with the double trigger to the same patients' previous IVF attempt, triggered with hCG-only.Results: Patients who received the double trigger (study group) had a significantly higher number of mature oocytes – MII (6.5 versus 3.6 p < 0.008), number of embryos transferred (2.4 versus 1.1 p < 0.03), a significantly higher proportions of MII oocytes per number of oocytes retrieved (69.7% versus 47.1% p < 0.03) and a higher number of top quality embryos (3.1 versus 1 p < 0.02), as compared to their previous control cycles (hCG-only trigger). Six pregnancies were recorded in the study group and none in the control group.Conclusions: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) improves IVF outcome in patients with high proportion of immature oocytes.

Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low rate of mature oocytes

Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation - 40 and 34 hours prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved.

Co-administration of GnRH-agonist and hCG for final oocyte maturation (double trigger) in patients with low number of oocytes retrieved per number of preovulatory follicles--a preliminary report.

BackgroundRecently, the co-administration of GnRH agonist and hCG for final oocyte maturation- 40 and 34 hours prior to OPU, respectively (double trigger) was suggested as the treatment of genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger improves the number of oocytes retrieved in patients with low (<50%) number of oocytes retrieved per number of preovulatory follicles.MethodsIn this proof of concept cohort historical study, we compared the stimulation characteristics of 8 IVF cycles, which include the double trigger to the patients’ previous IVF attempt, triggered with hCG-only.ResultsPatients who received the double trigger (study group) had a significantly higher number of oocytes retrieved, number of 2PN, number of embryos transferred and significantly higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, with a tendency toward a higher number of TQE, as compared to their previous cycles (hCG-only trigger). Three ongoing clinical pregnancies were recorded in the study group and none in the hCG-only trigger group.ConclusionsCo-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (double trigger), is suggested as a valuable new tool in the armamentarium for treating patients with low/poor oocytes yield despite an apparently normal follicular development and E2 levels and in the presence of optimal hCG levels on the day of OPU.

Successful Pregnancy Following Dual Triggering Concept (rhCG + GnRH Agonist) in a Patient Showing Repetitive Inmature Oocytes and Empty Follicle Syndrome: Case Report

After ovarian stimulation some oocytes collected for IVF cycles are arrest at the GV o MI stage at the time of retrieval despite controlled ovarian stimulation (COS) and a correct administration of hCG. However, it is unusual to have a complete failure of oocyte maturation after COS, especially in presence of normally growing follicles. Empty follicle syndrome (EFS) is a condition of uncertain etiology in which no oocytes are retrieved from apparently normally growing ovarian follicles with normal estradiol levels after ovarian stimulation for assisted reproductive techniques. In genuine EFS, dysfunction of the folliculogenesis seems to be the most plausible etiology. We report a case of primary infertility in which four consecutive IVF attempts yielded immature oocytes or EFS. Finally, at a fifth attempt the use of hCGr + GnRHa (dual triggering) for final follicular maturation resulted in a successful live birth. doi: http://dx.doi.org/10.4021/jmc1055w

The prevalence of genuine empty follicle syndrome

To describe the prevalence of "genuine" empty follicle syndrome (EFS) and "false" EFS at assisted reproductive technology (ART). Retrospective cohort. Large private fertility center. A total of 12,359 patients who underwent ART between 2004 and 2009. None. The failure to recover an oocyte during oocyte retrieval at ART, with and without adetectable serum β-hCG on the day of retrieval. Two cases of genuine EFS and nine cases of false EFS were identified in the cohort examined. The prevalence of genuine EFS was 0.016%, and the prevalence of false EFS was 0.072%. Only two out of 11 cases of EFS were considered genuine. Genuine EFS is a rare occurrence. Because this syndrome tends to recur with dismal pregnancy rates at ART, continued identification and further investigation of the syndrome are needed.

Recurrent genuine empty follicle syndrome

Failure to aspirate oocytes after ovarian stimulation for an in vitro fertilization cycle, after confirming normal folliculogenesis and steroidogenesis occurs in about 0.2–7% of the cycles. This condition is known as empty follicle syndrome. Most of the time, it may be due to human or pharmacological error, but rarely there is an entity called genuine empty follicle syndrome where no known cause can be identified.

The incidence of genuine empty follicle syndrome

OBJECTIVE: Rarely, no oocytes are retrieved from mature ovarian follicles after ovarian stimulation because of a condition known as empty follicle syndrome (EFS). EFS can be divided into two types: 1) false EFS where hCG is not administered properly; or 2) genuine EFS, a failure to retrieve oocytes despite optimal levels of β-hCG. The incidence and etiology of genuine EFS is unknown. The aim of this study was to determine the incidence of genuine EFS in a large cohort of patients and describe the clinical characteristics of these patients. DESIGN: Retrospective study. MATERIALS AND METHODS: All ART cycles at a single fertility center from year 2004 to 2009 comprised the study cohort, a total of 12,359 patients and 18,294 oocyte retrieval procedures. In order to exclude cases where an absence of oocytes was due to a poor response to stimulation or technical issues, only cases with 5 or more follicles with a diameter of at least 14mm on the day of hCG administration were included. Serum β-hCG levels were measured in cases where no oocytes were retrieved. RESULTS: A total of 46 cases of EFS were identified, representing an incidence of 0.25%. Only 2 patients had elevated serum β-hCG on the day of oocyte retrieval (124 and 61 mIU/mL). Both patients had primary infertility, with male factor as etiology for one patient, and PCOS for the other. Both patients had normal ovarian reserve. Neither patient used anti-inflammatory medications during stimulation. Both patients underwent 11 days of ovarian stimulation, with gonadotropin usage of 6225 and 674 IU, resulting in peak serum estradiol levels of 1730 and 2340 pg/ml, respectively. Neither patient underwent a subsequent ART cycle. No recurrent case was identified. The incidence of genuine EFS was 0.016% in this cohort. CONCLUSION: In this cohort of 12,359 patients, genuine EFS was very rare, and most cases were due to a failure to administer hCG. The etiology of genuine EFS warrants further investigation.

Poor prognosis in cycles following “genuine” empty follicle syndrome

Objectives The aim of this study was to investigate the prognosis in future IVF cycles of patients with empty follicle syndrome (EFS). Study design EFS cases and their future cycles were reviewed. Clinical pregnancy rate per started cycle was taken as the primary outcome in assessing the future outcome in IVF treatment cycles. Results A total of 3023 patients underwent 5238 IVF treatment cycles. Twenty-six patients (1%) had a total of 58 (1%) cycles of EFS. Thirteen women went through 32 further IVF treatment cycles following the diagnosis of EFS, yielding only two clinical pregnancies, giving a clinical pregnancy rate of 6.25% per started cycle. In addition, four patients had recurrence in a total of 15 cycles. Conclusions The occurrence of EFS will indicate poor IVF success in subsequent IVF cycles. Patients with “genuine EFS” should be counselled about the outcome of their future IVF cycles.

Immature Oocytes in “Apparent Empty Follicle Syndrome”: A Case Report

Empty follicle syndrome (EFS) is a condition in which no oocytes are obtained after an apparently successful ovarian stimulation. Genuine EFS (GEFS) is differentiated from false EFS by an optimal level of human chorionic gonadotropin on the day of oocyte retrieval. Some believe that GEFS does not exist and that it is only a reflection of the margin of error attendant upon the procedure of oocyte aspiration. Others believe that GEFS is caused by dysfunctional folliculogenesis, resulting in early atresia of oocytes. In this report, we present a case of apparent GEFS, in which immature oocytes were identified after filtration of follicular aspirates. Our findings suggest that delayed maturation of oocyte cumulus complexes in response to HCG might be an etiologic mechanism in some cases of GEFS. This creates a situation similar to the aspiration of immature follicles, where germinal vesicle-stage oocytes with dense scanty cumulus cells are often difficult to identify under a dissecting microscope.

Empty follicle syndrome: the reality of a controversial syndrome, a systematic review

To examine all case reports and studies of empty follicle syndrome (EFS) that have been published since the condition was first reported, in an attempt to identify trends or common features that may expose possible risk or causative factors. Systematic review of all available literature obtained from PubMed, Ovid, and Embase. Academic unit. Review of all published case reports and case studies. All original work was assessed and labeled as "genuine" or "false" EFS according to set definitions. Genuine and false EFS. We defined genuine EFS as a failure to retrieve oocytes from mature ovarian follicles after ovarian stimulation for IVF after apparently normal follicular development and steroidogenesis in the presence of optimal beta-hCG levels on the day of oocyte retrieval. False EFS included all cases in which this definition cannot apply and often in which human error or a pharmaceutical inaccuracy has occurred. By classifying all cases of EFS as "genuine" or "false" according to stated definitions, it was evident that a much greater proportion of cases of reported EFS, 67%, occurred as a result of human error and that "genuine empty follicle syndrome" is an even rarer event than previously presumed. Our report highlights the value of classifying cases of EFS as "genuine" or "false" and shows that more epidemiological data are required of "genuine" EFS cases to develop a clearer picture of the possible etiology.

Recurrent failure to recover oocytes supports the possibility of a genuine empty follicle syndrome

Empty follicle syndrome (EFS) is defined as the failure to recover oocytes during ovum pick-up in an otherwise apparently normal ovarian stimulation IVF cycle. The etiology of this phenomenon is often unknown, but it has been claimed to be related to technical problem following errors in human chorionic gonadotrophin (HCG) administration or defects in HCG batches. The occurrence of recurrent EFS has been suggested based on incidental case reports and may serve as proof that EFS may occasionally present a genuine syndrome.