Resistant Ovary Syndrome Research Articles

Testing the role of unstimulated ın vitro maturation in the developmental potential of immature oocytes in women with oocyte maturation abnormalities.

This study aims to investigate the developmental potential of immature oocytes and questions whether unstimulated in vitro maturation (IVM) can be used as a treatment in women with oocyte maturation abnormalities. This cohort study was conducted between September 2019 and December 2022, and it included 12 women who underwent unstimulated, non-hCG priming IVM.Oocytes were incubated in in vitro maturation medium for 26-48 hours and evaluated to compare their maturation profiles with the immature oocytes retrieved from the same patients in their previous IVF cycles. Among the twelve women in the study, eleven (91.6%) underwent whole exome sequencing (WES) analysis. Of these, ten women presented a total of 18 mutations, excluding Case 1, which had no previous mutation analysis. Of the mutations identified, 9 (50%) were located in the FSHR gene, 5 (27.8%) in the TUBB8 gene, 1 (5.6%) in the ZP1 gene, 1 (5.6%) in the SLFN14 gene, 1 (5.6%) in the AR gene, and 1 (5.6%) in the STEAP3 gene. Apart from one woman with resistant ovary syndrome,none of the women treated with unstimulated in vitro maturation had oocyte maturation . Remarkably, the only patient to achieve oocyte maturation in an unstimulated IVM cycle was Case 11, who had ROS and a single FSHR mutation. Unstimulated non hCG primed IVM has no value in the treatment of OMAS, except in cases with resistant ovary syndrome. However this study led our team to develop novel treatment options based on physiological mechanisms for some subtypes and supraphysiological approach for other subtypes of oocyte maturation abnormalities.

Resistant ovary syndrome: Two case reports and a literature review of effective controlled ovarian stimulation in IVF.

Resistant ovary syndrome (ROS) represents a rare reproductive endocrine disorder that is predominantly associated with infertility, characterized by heightened endogenous gonadotropin levels in the presence of a normal ovarian reserve. Patients with ROS typically exhibit a poor response to exogenous gonadotropins during controlled ovarian stimulation (COS). Due to the absence of a universally accepted effective COS protocol, this study aims to contribute to the existing body of literature by detailing 2 successful pregnancies achieved through conventional in vitro fertilization (c-IVF) in patients with ROS, and through retrospective analysis, seeks to elucidate the factors contributing to the successful ovarian stimulation in these cases, with the ultimate goal of establishing clinical guidelines for ROS management. The central challenge addressed in this study pertains to the effective induction of oocyte maturation during c-IVF COS in ROS patients. The study focuses on 2 infertile women diagnosed with ROS who sought to conceive via c-IVF. The patients were subjected to a COS protocol involving pituitary downregulation followed by ovarian stimulation using recombinant follicle-stimulating hormone (r-FSH) and human menopausal gonadotropin (HMG), preceded by 3 cycles of hormone replacement therapy (HRT) pretreatment. The proposed protocol elicited a favorable ovarian response, culminating in the retrieval of numerous mature oocytes and the development of multiple viable embryos via c-IVF, ultimately leading to successful live births post-embryo transfer. Our study suggests that the outlined COS protocol may serve as a viable treatment option for ROS patients aspiring to conceive through c-IVF, thereby potentially expanding the therapeutic repertoire for this challenging condition.

An update on the current indications for in vitro maturation.

In vitro maturation has become a significant component of modern assisted reproductive techniques. Published data have been supported for the safety and effectiveness of in vitro maturation treatment. In recent years, potential indications for in vitro maturation (IVM) have been a topic of interest and investigation. Significant improvements in technique enhancement and data publication for evaluating the efficacy of IVM have been achieved. Recent studies have shown that IVM could offer several advantages over in vitro fertilization. Currently, there are growing indications for IVM beyond the commonly mentioned indication of infertile women with polycystic ovary syndrome. Additionally, some potential candidates might have significant advantages for IVM, such as women diagnosed with gonadotropin resistance ovary syndrome or those seeking fertility preservation. With a better understanding of IVM, from basic science to clinical practice, it can be applied safely, effectively, and affordably to a broader range of patients, making it a more accessible and patient-friendly option. Despite the possibly acknowledged limitations, the potential of in vitro maturation cannot be denied. As this technique becomes increasingly accessible to patients and more continuous efforts are dedicated to advancing this technique, the impact of in vitro maturation is expected.

Disordered hypothalamus-pituitary-ovary axis in heterotopic extraovarian sex cord-stromal proliferation: a case report of fallopian tube serous adenofibroma

BackgroundFallopian tube serous adenofibromas are uncommon tumors of the female genital tract, only dozens of cases have ever been reported. Earlier study indicated that they might be derived from embryonic remnants of the Müllerian duct. Clinical presentation of these tumors is usually asymptomatic. Small cysts of 0.5–3 cm in diameter are mostly incidentally found at the fimbriae end, with coarse papillary excrescences lined by epithelial cells and connective tissue stroma without nuclear pleomorphism or mitosis.Case presentationA 23-year-old woman with normal secondary sexual characters and 46, XX karyotype, presented to the gynecology clinic complaining of irregular menstrual cycles. Laboratory studies reported unique discrepancy of hormone levels; anti-Müllerian hormone (AMH): 6.05 ng/mL (The normal range of AMH is 1.70–5.63 ng/mL in women aged under 35 years old), follicle stimulating hormone (FSH): 31.9 mIU/mL (reference range: 3.85–8.78, follicular phase; 4.54–22.51, ovulatory phase; 1.79–5.12, luteal phase; 16.74-113.59, menopause), and luteinizing hormone (LH): 52.0 mIU/mL (reference range: 2.12–10.89, follicular phase; 19.18-103.03, ovulatory phase; 1.20-12.86, luteal phase; 10.87–58.64, menopause), mimicking gonadotropin-resistant ovary syndrome. The ultrasound reported a right adnexal cyst of 10.4 × 7.87 × 6.7 cm. Laparoscopic evaluation was performed; pathology revealed serous adenofibroma of the fallopian tube with ovarian stroma contents. Heterotopic extraovarian sex cord-stromal proliferations was most probable. The patient’s hormone levels returned to the reproductive status two weeks after surgery; FSH: 7.9 mIU/mL, LH: 3.59 mIU/mL,and AMH: 4.32 ng/mL. The patient’s menstrual cycles have resumed to normal for over two years after removal of the fallopian tube cyst.ConclusionsThis case of fallopian tube serous adenofibromas presented a discrepancy of serum AMH and FSH mimicking gonadotropin-resistant ovary syndrome. The clinical picture derived from heterotopic extraovarian sex cord-stromal proliferation indicated a disordered hypothalamus-pituitary-ovary axis.

Application value of Early-Follicular Phase Long-Acting Gonadotropin-Releasing Hormone Agonist Long Protocol in patients with resistant ovary syndrome

BackgroundResistant ovarian syndrome(ROS) is a rare disease. It is difficult to diagnose and treat. Most of the literature reports on assisted pregnancy treatment for ROS patients are individual case reports. In this paper, the ovulation stimulation protocol and assisted pregnancy process of ROS infertile patients in our reproductive center were summarized and analyzed to provide information and support for the clinical treatment of ROS patients.MethodsFrom January 2017 to March 2022, assisted reproductive technology treatments and clinical characteristics parameters of six patients with ROS were retrospectively reviewed. Based on controlled ovarian stimulation protocols, these stimulation cycles were separated into four groups: Early-Follicular Phase Long-Acting Gonadotropin-Releasing Hormone Agonist Long Protocol (EFLL) group (n = 6), Progestin Primed Ovarian Stimulation(PPOS) protocol group (n = 5), mild-stimulation protocol group (n = 2), and Natural cycle protocol group (n = 3).ResultsA total of 16 cycles of ovulation stimulation were carried out in 6 patients with ROS. A total of 19 oocytes were retrieved, as well as 13 MII oocytes, 11 two pronuclear(2PN) fertilized embryos, and 8 excellent embryos. The oocytes acquisition rate was 50% and the fertilization rate of 2PN was 57.9%, and the excellent embryo rate was 72.7%. The EFLL protocol obtained 17 oocytes, 12 MII oocytes, 11 2PN fertilized embryos, and 8 excellent embryos; the mild-stimulation protocol obtained 1 oocyte; the Natural cycle protocol obtained 1 oocyte, and oocytes were not matured after in vitro maturation (IVM); the PPOS protocol obtained no oocytes. Compared with three other protocols, The fertilization rate of 2PN (64.7%) and excellent embryo rate (72.7%) in the EFLL protocol were higher than those of other protocols(0%). Two fresh cycle embryo transfers resulted in live births, while two frozen-thawed embryo transfer cycles resulted in one live birth and one clinical pregnancy using the EFLL protocol.ConclusionAlthough the current study is based on a small sample of participants, the findings suggest that the EFLL protocol can be employed for ovarian stimulation and may result in a live birth in ROS patients.

Identification and characterization of novel compound heterozygous variants in FSHR causing primary ovarian insufficiency with resistant ovary syndrome.

Primary ovarian insufficiency (POI) is among the foremost causes of women infertility due to premature partial or total loss of ovarian function. Resistant ovary syndrome (ROS) is a subtype of POI manifested as normal ovarian reserve but insensitive to gonadotropin stimulation. Inactivating variants of follicle-stimulating hormone receptor (FSHR), a class A G-protein coupled receptor, have been associated with POI and are inherited via an autosomal recessive pattern. In this study, we investigated the genetic causes of a primary infertility patient manifested as POI with ROS, and elucidated the structural and functional impact of variants of uncertain significance. Next-generation sequencing (NGS) combined with Sanger sequencing revealed novel compound heterozygous FSHR variants: c.1384G>C/p.Ala462Pro and c.1862C>T/p.Ala621Val, inherited from her father and mother, respectively. The two altered amino acid sequences, localized in the third and seventh transmembrane helix of FSHR, were predicted as deleterious by in silico prediction. In vitro experiments revealed that the p.Ala462Pro variant resulted in barely detectable levels of intracellular signaling both in cAMP-dependent CRE-reporter activity and ERK activation and displayed a severely reduced plasma membrane receptor expression. In contrast, the p.Ala621Val variant resulted in partial loss of receptor activation without disruption of cell surface expression. In conclusion, two unreported inactivating FSHR variants potentially responsible for POI with ROS were first identified. This study expands the current phenotypic and genotypic spectrum of POI.

Resistant ovary syndrome: Pathogenesis and management strategies.

Resistant ovary syndrome (ROS) is a rare and difficult gynecological endocrine disorder that poses a serious risk to women's reproductive health. The clinical features are normal sex characteristics, regular female karyotype, and usual ovarian reserve, but elevated endogenous gonadotropin levels and low estrogen levels with primary or secondary amenorrhea. Although there have been many case reports of the disease over the past 50 years, the pathogenesis of the disease is still poorly understood, and there are still no effective clinical management strategies. In this review, we have collected all the current reports on ROS and summarized the pathogenesis and treatment strategies for this disease, intending to provide some clinical references for the management and treatment of this group of patients and provide the foothold for future studies.

Unraveling the Puzzle: Oocyte Maturation Abnormalities (OMAS).

Oocyte maturation abnormalities (OMAS) are a poorly understood area of reproductive medicine. Much remains to be understood about how OMAS occur. However, current knowledge has provided some insight into the mechanistic and genetic origins of this syndrome. In this study, current classifications of OMAS syndromes are discussed and areas of inadequacy are highlighted. We explain why empty follicle syndrome, dysmorphic oocytes, some types of premature ovarian insufficiency and resistant ovary syndrome can cause OMAS. We discuss live births in different types of OMAS and when subjects can be offered treatment with autologous oocytes. As such, we present this review of the mechanism and understanding of OMAS to better lead the clinician in understanding this difficult-to-treat diagnosis.

Case report: Birth achieved after effective ovarian stimulation combined with dexamethasone in a patient with resistant ovary syndrome

BackgroundResistant ovary syndrome (ROS) is a rare endocrine disorder and there have been few reports of live births by affected patients. As gonadotropin resistance leads immature oocytes, some researchers reported few live births with in vitro maturation (IVM) of oocytes, but IVM is not always successful in ROS patients. Here, we report an original case of ROS, associated with Ig-FSHR in the serum, who achieved a live birth following ovarian stimulation combined with dexamethasone treatment.Case presentationThe 30-year-old woman presented with secondary amenorrhea and infertility. Her serum FSH levels were found to be higher than normal, but in discordance with a normal anti-Müllerian hormone (AMH) level and antral follicle count. Genetic investigation found no mutations potentially affecting FSHR. With reference of previous ROS studies, the patient’s serum was analyzed for antibodies directed against FSHR and dot blot analysis showed strong reactivity with FSHR. Then, dexamethasone was proposed to the patient, and she successfully became pregnant, finally delivering a healthy girl by caesarean section.ConclusionTo our best knowledge, this is the first report of the successful treatment of ROS using ovarian stimulation combined with dexamethasone. In some cases of ROS, high doses of exogenous gonadotropins in combination with immunosuppressive therapy could be an effective approach.

Oocyte maturation abnormalities - A systematic review of the evidence and mechanisms in a rare but difficult to manage fertility pheneomina.

A small proportion of infertile women experience repeated oocyte maturation abnormalities (OMAS). OMAS include degenerated and dysmorphic oocytes, empty follicle syndrome, oocyte maturation arrest (OMA), resistant ovary syndrome and maturation defects due to primary ovarian insufficiency. Genetic factors play an important role in OMAS but still need specifications. This review documents the spectrum of OMAS and to evaluate the multiple subtypes classified as OMAS. In this review, readers will be able to understand the oocyte maturation mechanism, gene expression and their regulation that lead to different subtypes of OMAs, and it will discuss the animal and human studies related to OMAS and lastly the treatment options for OMAs. Literature searches using PubMed, MEDLINE, Embase, National Institute for Health and Care Excellence were performed to identify articles written in English focusing on Oocyte Maturation Abnormalities by looking for the following relevant keywords. A search was made with the specified keywords and included books and documents, clinical trials, animal studies, human studies, meta-analysis, randomized controlled trials, reviews, systematic reviews and options written in english. The search detected 3,953 sources published from 1961 to 2021. After title and abstract screening for study type, duplicates and relevancy, 2,914 studies were excluded. The remaining 1,039 records were assessed for eligibility by full-text reading and 886 records were then excluded. Two hundred and twenty seven full-text articles and 0 book chapters from the database were selected for inclusion. Overall, 227 articles, one unpublished and one abstract paper were included in this final review. In this review study, OMAS were classified and extensively evaluatedand possible treatment options under the light of current information, present literature and ongoing studies. Either genetic studies or in vitro maturation studies that will be handled in the future will lead more informations to be reached and may make it possible to obtain pregnancies.

The Improvement and Clinical Application of Human Oocyte In Vitro Maturation (IVM).

Oocyte in vitro maturation (IVM) is a technology with a long history that was established before IVF. Although it has been studied extensively, the efficiency of IVM has been poor for almost 30 years. In terms of the benefits of IVM, the efficiency and adoption of IVM are being improved by some notable improvements that have occurred in recent years. The establishment of biphasic IVM is the most important advancement in recent years. Biphasic IVM includes the pre-IVM culturing phase and IVM phase. The CNP-mediated pre-IVM culturing system is specifically tailored for non/minimally stimulated immature oocytes, and its efficiency has been shown. This is the most significant improvement made in recent decades in this area. In the clinic, IVM can be used for PCOS patients to avoid the occurrence of ovarian hyperstimulation syndrome (OHSS). Additionally, this method can solve the reproductive problems of some patients with special diseases (resistant ovary syndrome) that cannot be solved by IVF. In most fertility preservation procedures, oocytes in small antral follicles are lost. However, IVM has the ability to capture this kind of oocyte and save reproductive potential. IVM can be easily combined with fertility preservation strategies that have been applied in the clinic and improve the efficiency of fertility preservation. IVM is a useful and attractive technology and may be used widely worldwide in the near future.

The live birth in a woman with resistant ovary syndrome after in vitro oocyte maturation and preimplantation genetic testing for aneuploidy.

We report the pregnancy and live birth achieved after in vitro maturation (IVM) of oocytes and PGT-A in a 23-year-old patient suffering from ovarian gonadotropin resistance. A woman with resistant ovary syndrome (ROS) had secondary amenorrhea, high FSH levels (25.34 mIU/mL) and LH (29.6 mIU/mL), low estradiol levels (15.2 pg/mL), and high serum AMH levels (38.0 ng/mL), associated with an increased antral follicle count (AFC) of 45. Without gonadotropin priming and HCG trigger, ultrasound-guided transvaginal oocyte retrieval was performed. Aspiration of antral-stage follicles allowed the retrieval of 15 immature oocytes. After oocyte collection, immature oocytes were cultured in the IVM medium. Following IVM, six of them reached metaphase II stage. Resultant matured oocytes were fertilized by intracytoplasmic sperm injection (ICSI). Embryos obtained were cultured to the blastocyst stage. On day 5, three embryos reached blastocyst stage. Trophectoderm biopsy and PGT-A were performed on two better quality embryos on day 5 after fertilization. Two biopsied embryos were reported to be euploid. PGT-A was performed utilizing next-generation sequencing (NGS\MPS). One embryo was transferred in an artificial thaw cycle and resulted in a viable intrauterine pregnancy and live birth. Our experience indicates that there is no requirement for gonadotropin stimulation and use of b-hCG trigger prior to IVM in patients with ROS. The results suggest that oocytes obtained with IVM in patients with ROS are capable of meiotic and mitotic division, fertilization, and generation of euploid embryos. IVM appears to be a valuable approach in patients with ROS, allowing them to have genetically connected offspring.

Синдром резистентных яичников и дозревание ооцитов в пробирке

Синдром резистентных яичников и дозревание ооцитов в пробирке

Hydrocortisone as a Potential Treatment of Savage Ovary Syndrome: A Rare Case from Syria

Advances in Medical, Dental and Health Sciences,2020,3,3,49-51.DOI:10.5530/amdhs.2020.3.12Published:October 2020Type:Case ReportAuthors:Dema Adwan Author(s) affiliations:Dema Adwan* Damascus University Gynecology and Obstetrics Hospital, SYRIA. Abstract:A 32-year old woman with a secondary amenorrhea for 5 years presented to my clinic (April 2019), previously had been treated as a premature ovarian failure patient and put on HRT. With further investigation, FSH Levels were high at the menopausal range, whereas the AMH levels and antral follicles count were within normal ranges and found to be age-compatible, These findings, as well as the failure of ovaries to respond to exogenous gonadotropins, helped to set the diagnosis of Savage Ovary Syndrome, which is also known as Insensitive Ovary Syndrome (IOS). Written informed consent was obtained from the patient for publication of this case report and accompanying images" Patient was convinced to be treated empirically with a high dose of Hydrocortisone and the result was the patient well responded as a normal spontaneous menstruation happened. The analysis of FSH and estradiol induces normal values and the return of the functional activity of the ovary to the formation of multiple ovarian bilateral follicle and give an echo feature similar to the ovarian hyper stimulatory syndrome with an increase the thickness of the endometrium. This case shows the importance of further studying patients with secondary amenorrhea and high levels of gonadotropins and not to treat them all as premature ovary insufficiency patients, just like our patient was firstly treated for a long time. Furthermore, the case highlights the potential benefit of the treatment of Savage Ovary Syndrome patients with Hydrocortisone. Keywords:Antral follicles, Gonadotropin, Infertility, Insensitive ovary, Resistant ovarian syndrome, Secondary amenorrheaView:PDF (535.52 KB)

Surgical approaches of drug-free in vitro activation and laparoscopic ovarian incision to treat patients with ovarian infertility

To demonstrate our procedures of drug-free invitro activation (IVA) for treating patients with premature ovarian insufficiency (POI) or diminished ovarian reserve (DOR), as well as the laparoscopic ovarian incision (LOI) procedure for treating patients with resistant ovary syndrome (ROS). Step-by-step video demonstration of the surgical procedures. Fertility clinic and reproductive medicine department. Women were diagnosed with POI based on recent amenorrhea before 40 years of age or with DOR according to the Bologna criteria, showing growth of a few antral follicles after ovarian stimulation. ROS patients were diagnosed based on amenorrhea with hypergonadotropic hypoestrogenism but showing age-appropriate number of antral follicles under transvaginal ultrasound. The drug-free IVA consists of the following 4 steps: removing a part of the cortex from one or both ovaries; cutting ovarian cortical pieces into small cubes invitro; making pockets for ovarian tissue grafting; and grafting ovarian cortical cubes. The LOI procedure consisted of only one step: cutting ovarian cortex in situ. Both procedures were followed by ovarian hyperstimulation for at least 1 year. Informed consent was obtained from patients and approval was granted by the Biomedical Ethics Committee of the International University School of Medicine and the Rose Ladies Clinic. The present clinical trial was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). Follicle growth. These procedures can be completed within 1 hour under laparoscopic surgery. There were no complications. In 13 of 15 patients treated with drug-free IVA, increases in antral follicle numbers were found, followed by a higher number of retrieved oocytes for invitro fertilization. In addition to one spontaneous pregnancy, embryo transfer allowed four live births and one ongoing pregnancy. Five additional patients and one miscarriage patient have cryopreserved embryos for future transfer. We also found follicle growth to the preovulatory stage in seven of 11 ROS patients who have not responded to any endogenous and exogenous follicle-stimulating hormone stimulations for follicle growth prior to LOI treatment, allowing the retrieval of mature oocytes for invitro fertilization. Four ROS patients became pregnant, followed by the delivery of three healthy infants and one ongoing pregnancy. A drug-free IVA approach provided an infertility treatment for recent POI or DOR patients. This procedure promoted growth of residual ovarian follicles following ovarian tissue fragmentation invitro, leading to Hippo signaling disruption. Although ROS patients exhibited symptoms of hypergonadotropic hypoestrogenism similar to that of POI patients, they still had multiple secondary follicles. Hippo signaling disruption invivo based on cutting ovarian cortex using LOI could promote follicle growth. UMIN000029807.

Gonadotropin-Resistant Ovary Syndrome Presented with Secondary Amenorrhea and Infertility: A Case Report.

Resistant ovary syndrome (ROS) is a presentation of hypergonadotrophic hypogonadism condition with very low incidence. Infertility is one of the most common complaints of women with this syndrome. We herein present a case of a 27-year-old woman with all features of secondary amenorrhea and secondary sexual characteristics. In 2018, the patient was referred to the Hazret-e-Zeinab Infertility Center affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. She was diagnosed with secondary amenorrhea and increased gonadotropin secretion after menopause. However, the patient had a normal antral follicle count, anti-Müllerian hormone level, 46, XX karyotype, and thyroid function. After taking oral contraceptives her menstruation started, but she showed no response to high doses of exogenous gonadotropins. She was advised to have an embryo derived from in vitro maturation. By using patients' own oocyte maturation, this technique could be a better treatment for infertile women with ROS. This case report is particularly interesting due to the rarity of its prevalence and similarity with primary ovarian insufficiency.

Resistant Ovary Syndrome Masquerading as Premature Ovarian Insufficiency

Premature ovarian insufficiency (POI) is typically the end result of premature depletion of primordial follicles. However gonadotropin-resistant ovary syndrome could result in a similar clinical and laboratory picture with a more favorable outcome. A 29-year-old G0 woman with POI referred to our infertility clinic for egg donation. On ultrasound, her ovaries contained multiple resting antral follicles (AFs). Patient underwent transvaginal ultrasound-guided follicle aspiration of all visible small antral follicles. Eggs were in vitro matured and resulting embryos cryopreserved. Patient achieved a successful live birth with her own eggs. Gonadotropin-resistant ovary syndrome must be considered in all women diagnosed with hypergonadotropic hypogonadal POI and normal antral follicle count (AFC) and anti-Mullerian hormone (AMH). In these patients, pregnancy can be achieved with their own eggs. J Clin Gynecol Obstet. 2019;8(4):111-113 doi: https://doi.org/10.14740/jcgo575

Resistant Ovary Syndrome Masquerading as Premature Ovarian Insufficiency

Resistant Ovary Syndrome Masquerading as Premature Ovarian Insufficiency

In vitro maturation (IVM) of oocytes in patients with resistant ovary syndrome and in patients with repeated deficient oocyte maturation.

To assess the efficiency of IVM in patients with repeated ART failure due to resistant ovary syndrome or due to deficient oocyte maturation. Clinical and laboratory data were obtained retrospectively from 28 patients who underwent 49cycles of IVM between 2010 and 2017; nine patients had resistant ovary syndrome and 19 patients had repeated deficient oocyte maturation. Nine patients with resistant ovary syndrome underwent 24 IVM cycles. In those, an average of 11.5 ± 10.4 cumulus-oocyte complexes (COC) was retrieved, and IVM resulted in 3.4 ± 3.1 mature oocytes. After ICSI and transfer of 23 cleavage-stage embryos, eight pregnancies were obtained, resulting in five healthy live births. The live birth rate was 16.7% per started cycle and 33.3% per patient. Nineteen patients with a history of deficient oocyte maturation underwent 25 IVM cycles. An average of 10.6 ± 9.2 COC was retrieved, and after IVM, 1.3 ± 2.1 oocytes were mature. No mature oocytes were obtained in 11cycles. In ten cycles with mature oocytes, none of them fertilized after ICSI. Out of four cycles with fertilized oocytes, only one good-quality embryo was obtained. No live births were obtained after IVM in patients with a history of deficient oocyte maturation. Based on our experience, IVM is a valuable approach in patients with resistant ovary syndrome, but should not be recommended for patients with deficient oocyte maturation.

Study of two Chinese families affected with resistant ovarian syndrome resulted from novel mutations of FSHR gene

To explore the genetic etiology for two Chinese families affected with hypergonadotropic amenorrhea and normal number of antral follicles. Peripheral venous blood samples were collected from the families for the extraction of genomic DNA. Mutations of FSHR and LHCGR genes were screened using PCR and Sanger sequencing. Suspected pathogenic mutations were verified in other members of the families. Bioinformatics software and NCBI were used to analyze the pathogenicity of the mutations. Two previously unreported homozygous mutations, c.419delA and c.1510C>T of the FSHR gene were found in the probands of family I and II, respectively. Pedigree and bioinformatics analysis suggested that both mutations were pathogenic. Literature review suggested that both families were affected with resistant ovary syndrome rather than premature ovarian failure. Two novel mutations of the FSHR gene have been identified, which have enriched the spectrum of FSHR gene mutations and provided a basis for genetic counseling and direction for reproduction.