Intermittent spontaneous ovulation in patients with premature ovarian failure: Three case reports and review of literature.

BACKGROUND: Premature ovarian failure (POF) is the end-stage of a decline in ovarian function prior to the age of 40 years that involves symptoms associated with low estradiol (E2) levels and a minimal probability of pregnancy. This increases the physical and psychological burden experienced by young women of reproductive age, particularly with regards to over-diagnosis. CASE SUMMARY: Here, we report three cases (29, 22, and 33 years-of-age) diagnosed with POF after experiencing secondary amenorrhea for more than one year, serum levels of follicle-stimulating hormone (FSH) > 40 IU/L on two occasions with an interval of more than 4 wk, and negative progesterone withdrawal tests. All three patients were intermittently administered with drugs to create an artificial cycle. During the subsequent discontinuation period, the patients experienced intermittent follicular growth and spontaneous ovulation. One patient experienced two natural pregnancies (both with embryo arrest). CONCLUSION: Our findings suggest that young patients with POF can experience unpredictable and intermittent spontaneous follicular development, ovulation, and even natural pregnancy. Clinicians should provide appropriate medical guidance and individualized treatments according to fertility requirements, genetic risks and hypoestrogenic symptoms as soon as possible.

Therapeutic Effect of Melatonin in Premature Ovarian Insufficiency: Hippo Pathway Is Involved.

Objective: Premature ovarian insufficiency (POI) is a female reproductive disorder of unknown etiology with no definite pathogenesis. Melatonin (MT) is an endogenous hormone synthesized mainly by pineal cells and has strong endogenous effects in regulating ovarian function. To systematically explore the pharmacological mechanism of MT on POI therapy, a literature review approach was conducted at the signaling pathways level. Methods: Relevant literatures were searched and downloaded from databases, including PubMed and China National Knowledge Infrastructure, using the keywords "premature ovarian insufficiency," "Hippo signaling pathways," and "melatonin." The search criteria were from 2010 to 2022. Text mining was also performed. Results: MT is involved in the regulation of Hippo signaling pathway in a variety of modes and has been correlated with ovarian function. Conclusions: The purpose of this review is to summarize the research progress of Hippo signaling pathways and significance of MT in POI, the potential crosstalk between MT and Hippo signaling pathways, and the prospective therapy.

Pregnancy Outcomes of In Vitro Fertilization with or without Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study in Chinese Patients.

BACKGROUND: The effect of ovarian hyperstimulation syndrome (OHSS) on pregnancy outcomes of in vitro fertilization (IVF) patients is still ambiguous. This study aimed to analyze pregnancy outcomes of IVF with or without OHSS in Chinese patients. METHODS: A retrospective cohort study was undertaken to compare pregnancy outcomes between 190 women with OHSS and 197 women without OHSS. We examined the rates of clinical pregnancy, multiple pregnancies, miscarriage, live birth, preterm delivery, preterm birth before 34 weeks' gestation, cesarean delivery, low birth weight (LBW), and small-for-gestational age (SGA) between the two groups. Odds ratios (OR s) and 95% confidence intervals (CI s) of measure of clinical pregnancy were also analyzed. RESULTS: The clinical pregnancy rate of OHSS patients was significantly higher than that of non-OHSS patients (91.8% vs. 43.5%, P < 0.001). After controlling for drug protocol and causes of infertility, the adjusted OR s of moderate OHSS and severe/critical OHSS for clinical pregnancy were 4.65 (95% CI, 1.86-11.61) and 5.83 (95% CI, 3.45-9.86), respectively. There were no significant differences in rates of multiple pregnancy (4.0% vs. 3.7%) and miscarriage (16.1% vs. 17.5%) between the two groups. With regard to ongoing clinical pregnancy, we also found no significant differences in the rates of live birth (82.1% vs. 78.8%), preterm delivery (20.9% vs. 17.5%), preterm birth before 34 weeks' gestation (8.6% vs. 7.9%), cesarean delivery (84.9% vs. 66.3%), LBW (30.2% vs. 23.5%), and SGA (21.9% vs. 17.6%) between the two groups. CONCLUSION: OHSS, which occurs in the luteal phase or early pregnancy in IVF patients and represents abnormal transient hemodynamics, does not exert any obviously adverse effect on the subsequent pregnancy.

Factors Associated with Effectiveness of Treatment and Reproductive Outcomes in Patients with Thin Endometrium Undergoing Estrogen Treatment.

BACKGROUND: Thin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endometrial thickness (EMT). The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium. METHODS: Relevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected. Possible factors influencing the effectiveness of treatment were analyzed retrospectively by logistic regression analysis. Eighty-seven infertile women without thin endometrium who had undergone assisted reproduction served as controls. The cases and controls were matched for age, assisted reproduction method, and number of embryos transferred. Reproductive outcomes of study and control groups were compared using Student's t-test and the Chi-square test. RESULTS: At the end of estrogen treatment, EMT was ≥8 mm in 93/101 patients (92.1%). Effectiveness of treatment was significantly associated with maximal pretreatment EMT (P = 0.017) and treatment duration (P = 0.004). The outcomes of assisted reproduction were similar in patients whose treatment was successful in increasing EMT to ≥8 mm and the control group. The rate of clinical pregnancy in patients was associated with the number of good-quality embryos transferred in both fresh (P = 0.005) and frozen-thawed (P = 0.000) embryo transfer cycles. CONCLUSIONS: Thinner EMT before estrogen treatment requires longer treatment duration and predicts poorer treatment outcomes. The effectiveness of treatment depends on the duration of estrogen administration. Assisted reproductive outcomes of patients whose treatment is successful (i.e., achieves an EMT ≥8 mm) are similar to those of controls. The quality of embryos transferred is an important predictor of assisted reproductive outcomes in patients treated successfully with exogenous estrogen.

[Clinical study on 48 cases with complete 17α-hydroxylase deficiency].

OBJECTIVE: To investigate efficient diagnosis and treatment of 17α-hydroxylase (17OHD) deficiency by summarizing clinical characteristics of those patients. METHODS: From January 1983 to January 2010, 48 cases with 17OHD in Peking Union Medical College Hospital were studied retrospectively. RESULTS: Among 48 patients with 17OHD, karyotype analysis showed, 12 cases with 46, XX and 36 cases with 46, XY. The 46, XX karyotype and 46, XY karyotype with complete 17OHD had typical clinical presentation of amenorrhea[12/12, 100% (36/36)], no typical spontaneous puberty [12/12, 13.9% (5/36)], Hypertension [11/12, 100% (36/36)], hypokalemia [K(+): (2.6 ± 0.7), (2.8 ± 0.7) mmol/L], hypergonadotropin [follicle-stimulatinghormone (FSH): (51 ± 35), (79 ± 46) U/L, luteinizing hormone (LH): (27 ± 14), (49 ± 37) U/L], impaired production of sex hormones [testosterone (T): 0.003, 0.005 nmol/L; estradiol (E(2)): 26.86, 10.64 pmol/L], hyper-progesterone[ (P): (32 ± 15), (29 ± 23) nmol/L], impaired production of 17α-hydroxyprogesterone (17α-OHP)[(2.5 ± 1.1), (2.4 ± 1.7) nmol/L], ACTH hypersecreation (91.8, 114.0 pmol/L). ACTH stimulating test did not elevated in 17α-OHP and cortisol. CONCLUSION: When patients with elevated basal serum levels of progesterone higher than that of ovulation period in addition to clinical symptoms, examination about 17OHD should be warranted.

[Treatment of malignant ovarian germ cell tumors with relapse or failed in primary therapy].

OBJECTIVE: To study the clinical characteristic, the optimal treatments and the prognosis for the recurrence and failure of primary treatment in malignant ovarian germ cell tumors (MOGCT). METHODS: The clinical data of 17 recurrent and failure of primary treatment in MOGCT cases treated in Pecking Union Medical College Hospital from January 1983 to May 2008 were analyzed retrospectively to evaluate failure of primary treatment and second treatment. RESULTS: Only the 4 cases of recurrent and failure of primary treatment of MOGCT were underwent comprehensive surgical staging. After primary surgery in 1 - 8 months, 16 cases received the non-standard chemotherapy were found the lesion again. The secondary debulking surgery was done for the 15 cases and also received the standard chemotherapy. Among of them, 8 cases were survival during follow up, 5 cases gave up the treatment and 4 patients were lost following up during the treatment. CONCLUSIONS: The standard primary treatment is the most important for the MOGCT. Even for the recurrence and failure of primary treatment of MOGCT, the satisfied cytoreductive surgery plus the standard chemotherapy also show the significant impact on the prognosis.

[Clinical analysis of thirteen cases of hypersensitivity reactions to carboplatin.].

OBJECTIVE: To characterize hypersensitivity reactions to chemotherapy with carboplatin in patients with gynecologic malignancies and serve use of carboplatin. METHODS: We retrospectively analyzed the clinical features, management, or outcome of carboplatin-related hypersensitivity reactions in 13 patients with gynecologic malignancies from 1983 to 2008. RESULTS: Twenty times hypersensitivity reactions happened in thirteen women with carboplatin hypersensitivity reactions. The earliest one was at the 5th cycle, the last one was at the 28th cycle; the average cycle was 11.6. The accumulative dosage of carboplatin was 1 900 - 11 400 mg. The average dose was 4840 mg, 2500 - 7200 mg were the main dose range. More than 5 cycles and (or) more than 2500 - 7200 mg of carboplatin administration significantly increased the incidence of hypersensitivity reactions in the twelve patients. Reactions were generally occurred at the first 5 - 10 minutes during intravenous infusion. The average time was 7.6 minutes. Symptoms included mild-to-moderate reactions and severe reactions. Thirteen patients experienced carboplatin hypersensitivity. Two out of 13 cases exhibited severe hypersensitivity reaction at the first time. The first hypersensitivity reactions was mild-to-moderate in 11 cases. When retreated with carboplatin, 4 exhibited no more reactions, 5 exhibited mild-to-moderate hypersensitiviry reactions, 2 exhibited severe reactions. Mild-to-moderate reactions were resolved by temporary interruption of carboplatin infusion, and (or) using steroid, while severe hypersensitivity reactions were resolved by more medicines. CONCLUSIONS: The hypersensitivity reactions in the patients receiving carboplatin are increased after multiple doses of the agent. The possible of retreat with the carboplatin for the mild-to-moderate reactions may be considered. Hypersensitivity reactions should be treated actively. The following chemotherapy should be planed individually. The primary chemotherapy protocol for the patients with severe hypersensitivity reactions should not be reconsidered.

[Clinical analysis of 30 patients with perineal endometriosis].

OBJECTIVE: To investigate the diagnosis and treatment of perineal endometriosis. METHODS: The clinical date of 30 patients with perineal endometriosis, aged 32.3 (23 approximately 44), who were admitted 1983 - 2006, operated on, and followed up for 0.5 approximately 13 years, were analyzed. RESULTS: The incidence of perineal endometriosis was 0.32% among the total endometriosis cases. Five of these 30 patients (16.7%) suffered from perineal endometriosis combined with pelvic endometriosis. The latent period was 4 months to 13 years. There was no significant difference in onset of age. All patients had cyclical and painful lesions. The level of CA125 was normal. All patients were cured after complete surgical excision. CONCLUSION: Diagnosis of perineal endometriosis can be made based on the patients' history and clinical manifestations. Surgical excision is the first choice of treatment. The recurrent rate of the cases without anal sphincter involvement is lower than that with anal sphincter invasion since the complete incision can be made. It is important to evaluate pre-operatively if the anal sphincter is involved.

[The chick embryo chorioallantioc membrane as a model for in vivo research on anti-angiogenesis in endometriosis].

OBJECTIVE: To establish the chick embryo chorioallantioc membrane (CAM) as a model for in vivo research on endometriosis. The model was used to investigate the mechanism of anti-vascular endothelial growth factor (VEGF) antibody for treatment of endometriosis. METHODS: Human endometrial fragments were explanted onto the CAM. Then anti-VEGF antibody was used for the endometriosis-like lesions after transplantation of human endometrial fragments. The CAM models were treated respectively as control groups and experimental groups. The terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were used in vivo for analysis of anti-angiogenesis. RESULTS: The apoptosis intensity of anti-VEGF antibody treated groups (6.7 +/- 0.9, 6.9 +/- 0.8) was significantly higher than that of the control groups (5.0 +/- 0.9, 5.4 +/- 1.1; P < 0.05). The proliferation intensity was not different in these groups. Lower MVD was observed in experimental groups [(4.2 +/- 1.1), (4.9 +/- 1.2) vessels] than the control groups [(6.9 +/- 1.6), (9.1 +/- 3.0) vessels; P < 0.05]. CONCLUSIONS: CAM is an extraembryonic membrane that is commonly used in vivo for the study of angiogenesis and anti-angiogenesis. Anti-VEGF antibody can be used to accelerate apoptosis of the endometrial cells and vascular endothelium cells, but it has no effect on the proliferation of these cells.

[Expression of vascular endothelial growth factor receptors in the ectopic and eutopic endometrium of women with endometriosis].

OBJECTIVE: To study the localization and expression of the vascular endothelial growth factor receptors (VEGFR) Fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing receptor (KDR) in human ectopic and eutopic endometrium of patients with endometriosis. METHODS: Specimens of endometriosis patients, aged (38 +/- 8) years, including 37 specimens of entopic endometrium, 34 specimens of ovarian chocolate cyst, 34 specimens of ovarian chocolate cyst, 15 specimens of red peritoneal endometriosis lesions, and 4 abdominal wall endometriosis lesions were collected. Specimens of endometrium of 33 patients with other gynecological diseases, aged (36 +/- 8) years, were collected during operation and used as controls. Immunohistochemistry was used to detect the location and expression of Flt-1 and KDR protein in different tissues. Western blotting was used to detect the protein expression of Flt-1 and KDR protein in different tissues. The mRNA expressions of Flt-1 and KDR were detected by RT-PCR. RESULTS: Flt-1 and KDR were expressed in the endometrial glandular epithelium and stromal cells besides the endometrial blood vessels. The positive expression rate of Flt-1 and KDR in the ectopic endometrium of endometriosis patients were 94.3% and 91.4% respectively, both significantly higher than those in the ovarian endometrial cyst (74.3% and 77.1% respectively, both P < 0.05), and similar to those in the eutopic endometrium of the endometriosis patients (93.8% and 90.6% respectively, both P > 0.05). In the eutopic endometrium of the endometriosis patients, the Flt-1 mRNA expression level was 2.4 +/- 1.2 and the Flt-1 protein expression level was 31 +/- 17, and the KDR mRNA expression level was 3.0 +/- 1.4 and the KDR protein expression level was 36 +/- 24, all significantly higher than those in the ovarian endometrial cyst (1.5 +/- 0.9 and 1.8 +/- 1.0 for the Flt-1 and KDR mRNA expressions, and 17 +/- 6 and 20 +/- 11 for the Flt-1 and KDR protein expressions, all P < 0.05), and similar to those in the eutopic endometrium of the non-endometriosis patients (1.9 +/- 0.8 and 2.3 +/- 1.3 for the Flt-1 and KDR mRNA expressions, and 24 +/- 18 and 25 +/- 16 for the Flt-1 and KDR protein expressions, all P > 0.05) CONCLUSION: VEGF may play certain biological role in the development of endometriosis through VEGFR (Flt-1 and KDR). The expression of Flt-1 and KDR in the endometriotic lesion appears to be associated with neovascualization.

[Clinical study about diagnosis and management on 10 women with rectovaginal endometriosis].

OBJECTIVE: To study the diagnosis and therapy of the rectovaginal endometriosis. METHODS: Descriptive retrospective study, between 1992 and 2002, 10 women with rectovaginal endometriosis were treated at the Peking Union Medical College Hospital. RESULTS: The average age were 40 years old. Six patients presented with rectal irritative symptom. Three of them complained about deep dyspareunia. Eight patients complained about mild to moderate dysmenorrhea. The recto-vaginal septum should be carefully palpated. None of these patients had either clinical or objective evidence of ovarian endometriosis, nor was there evidence of any obstructive lesions of the intestine or ureters. The CA(125) levels had a sensitivity of 20%. Ultrasonography failed to find the rectovaginal endometriotic nodules. Diagnosis of the rectovaginal endometriosis was based on symptoms, vaginal and rectal examination. The Revised American Fertility Society (rAFS) stages can not evaluate the grade of the endometriosis. Four patients were given leuprolide acetate depot at 3.75 mg, 1 ampule every 28 days, and treatment had a planned duration of 3 mouths. Follow-up evaluations were set 3 mouths later. The patients showed an improvement with respect to pain during the 3 mouths treatment course but had early pain recurrence after drug suspension. The endometriotic lesions showed a slight but reduction in size during therapy but had returned to original volume within 3 mouths after cessation of the gonadotropin-releasing hormone analog (GnRH-a) treatment. Finally, all patients required further treatment with a surgical solution. Six patients succeeded to remove the nodules by laparotomy. Four patients were failed to remove the total lesions by laparoscope and transvaginal section. CONCLUSIONS: The vaginal and rectal examination should be performed if the patients complained about tectal irritative symptom or dyspareunia. The rAFS stages had no strong association with the severity of the rectovaginal endometriosis. GnRH-a should not be considered a real therapeutic alternative to surgical treatment for patients with symptom endometriosis of rectovaginal septum. Laparotomy is efficient for the treatment of the rectovaginal endometriosis.