Intramuscular injection of human chorionic gonadotropin prior to secretory transformation in patients undergoing frozen-thawed embryo transfer cycles.

BACKGROUND: The major difference between a natural cycle and an artificially prepared cycle is the lack of luteinizing hormone (LH) peak in the latter. The LH/hCG receptors were identified to express in human endometrium and evidences of experiments also suggested the beneficial role of hCG in embryo implantation, indicating that the LH peak might be of clinical significance and the activation of LH/hCG receptors in the endometrium could improve embryo implantation. Hence, we postulated that the addition of hCG prior to secretory transformation in an artificial cycle might improve pregnancy outcomes. METHODS: This retrospective cohort study was conducted at a Reproductive Medicine Center between 2016 and 2018. Patients aged ≤43 years at the (index) oocyte retrieval and undergoing artificially prepared frozen-thawed embryo transfer (FET) with at least one good-quality embryo transferred were included. The cycles were divided into two groups: The hCG group (n = 337) received an intramuscular injection of 10,000 IU hCG before secretory transformation; the control group (n = 364) performed FET without hCG administration. The primary endpoint was live birth delivery rate (LBR), secondary outcomes included implantation rate, clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR). RESULTS: The LBR (49.9% vs 39.6%, P < 0.01), CPR (61.4% vs 50.5%, P < 0.01) and OPR (52.8% vs 43.1%, P < 0.05) were statistically significantly higher in the hCG group than the control group. The superiority in LBR after hCG administration remained significant after adjusting for confounding factors (OR 1.613, 95% CI 1.173-2.217; P < 0.01). In the subgroup analysis, the improvement in LBR was statistically significant after hCG administration for cleavage-stage embryo transfer cycles (51.2% vs 42.3%, P < 0.05), whereas for blastocyst transfer cycles, the improvement in LBR was not (45.7% vs 31.3%, P > 0.05). CONCLUSIONS: Intramuscular hCG injection prior to secretory transformation may benefit LBR in patients undergoing artificially prepared FET cycles. But it should be noted that nonsignificant tendency towards higher LBR was observed after hCG administration in patients undergoing blastocyst transfer. So, future prospective randomized controlled studies are required to confirm, especially for blastocyst transfer cycles.

Down-regulation of long non-coding RNA MALAT1 inhibits granulosa cell proliferation in endometriosis by up-regulating P21 via activation of the ERK/MAPK pathway.

STUDY QUESTION: Is there a specific mechanism underlying the association between lung adenocarcinoma transcript 1 (MALAT1) and endometriosis-related infertility? SUMMARY ANSWER: The down-regulation of MALAT1 in endometriosis granulosa cells (GCs) may have an adverse effect on the growth and development of oocytes by inhibiting GC proliferation, due to cell cycle-dependent mechanisms that enhance P21 expression through activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway. WHAT IS KNOWN ALREADY: The association between endometriosis and infertility is well supported throughout the literature, and endometriosis per se and its surgical treatment have an adverse effect on the ovarian reserve and on oocyte development. MALAT1, one of the most extensively expressed and evolutionarily conserved transcripts, has been implicated to play a role in human development and many diseases. However, little is known about the role of MALAT1 long non-coding RNA (lncRNA) in endometriosis and its associated infertility. STUDY DESIGN, SIZE, DURATION: We measured MALAT1 lncRNA expression levels in GCs from 52 endometriosis patients and 52 controls. Also, MALAT1 was knocked down in a human GC tumor-derived cell line, KGN, to investigate the role of MALAT1 and its molecular mechanism in cell proliferation. PARTICIPANTS/MATERIALS, SETTING, METHODS: GCs were collected from women with or without endometriosis undergoing IVF or ICSI treatment. All endometriosis patients were diagnosed by laparoscopy or laparotomy, and control patients were limited to male factor or tubal disease and had a normal ovarian reserve. Quantitative real-time PCR (qRT-PCR) was used to measure the differential expression levels of MALAT1 lncRNA between endometriosis patients and controls. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic values of MALAT1 in endometriosis. In the KGN cell line, MALAT1 was knocked down with locked nucleic acid GapmeRs. Cell counting kit-8 assays, ethynyl-2-deoxyuridine assays and flow cytometry were used to study the role of MALAT1 in cell proliferation and cell-cycle progression, and western blotting was performed to detect the potential underlying mechanism. MAIN RESULTS AND THE ROLE OF CHANCE: We first found that MALAT1 lncRNA was significantly down-regulated in endometriosis GCs and was associated with the antral follicle count (R = 0.376, P < 0.001 versus control). In addition, MALAT1 lncRNA levels were significantly lower in the GCs of infertile women with advanced stages of endometriosis (P = 0.01 versus control). The ROC curves illustrated strong separation between all the endometriosis patients and the control group (AUC: 0.705; 95% CI: 0.606-0.804; P < 0.001), Stage I-II and control group (AUC: 0.651; 95% CI: 0.536-0.767; P = 0.016), and Stage III-IV and control group (AUC: 0.827; 95% CI: 0.718-0.936; P < 0.001). MALAT1 lncRNA was primarily localized in the nuclei of GCs. We found a negative correlation between MALAT1 lncRNA and P21 mRNA in the GCs from patients (R = -0.628; P < 0.001). MALAT1 knockdown in KGN cells inhibited cell proliferation and cell-cycle progression. In addition, MALAT1 knockdown induced an increase in both the mRNA and protein levels of P21, and of P53, phosphorylated ERK1/2 (p-ERK1/2) and phosphorylated c-Jun N-terminal protein kinase (p-JNK) protein levels, as well as causing a decrease in cyclin dependent kinase 2 (CDK2), cyclin D1 and p-P38 MAPK protein levels. Furthermore, inhibition of the ERK/MAPK pathway with U0126, the up-regulation of p-ERK1/2, P21 and P53, and the down-regulation of CDK2 and cyclin D1 by the knockdown of MALAT1 were all attenuated by MALAT1 knockdown. Therefore, MALAT1 may regulate GC proliferation through P21/P53-dependent control of the cell cycle, and the ERK/MAPK pathway participates in this process. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: The hormonal treatment used in IVF and surgical removal of endometriotic lesions may have altered MALAT1 expression in GCs. The ovarian granulosa-like tumor cell line, KGN, was used for further functional and mechanistic studies due to the difficulties in obtaining human GCs in sizable amounts and maintaining primary cultures. WIDER IMPLICATIONS OF THE FINDINGS: Our finding represents the first example of an lncRNA-based mechanism in endometriosis GCs. Women with endometriosis show altered MALAT1 expression levels in GCs that may impair fertility by regulating the function of GCs. Therefore, analysis of MALAT1 and its molecular mechanisms of action provide new insights into the pathogenesis of endometriosis and its associated infertility. STUDY FUNDING/COMPETING INTEREST(s): This work was supported by the National Natural Science Foundation of China (grant number: 81671524) and the National key research and development program of China (grant number: 2017YFC1001100). The authors declare there is no conflict of interest.

Retrospective analysis of reproductive outcomes in women with primary ovarian insufficiency showing intermittent follicular development.

The aim of this retrospective study was to explore the reproductive outcomes of IVF treatment in women with primary ovarian insufficiency (POI) showing intermittent follicular development. A total of 44 POI women with normal karyotype and absent autoimmunity, attending the centre for fertility treatment at Nanfang Hospital, Guangzhou from March 2009 to March 2011, were identified as suitable for inclusion in this study. Out of 44 women, 20 (20/44; 45.5%) had growing follicles and 13 underwent 27 oocyte retrievals. The empty follicle rate per oocyte retrieval was 70.4% (19/27); eight oocytes were recovered: one (12.5%) germinal vesicle (GV), two (25.0%) metaphase I (MI), one (12.5%) metaphase II (MII), and four (50.0%) atretic. One MI oocyte matured in vitro and two women had embryo transfer. Only the woman with the MI oocyte matured in vitro conceived, giving birth to a healthy baby at term. These results suggest that intermittent follicular development is common in women with POI but most of the developed follicles are empty or contain atretic oocytes. The pregnancy rate remains very low for IVF treatment.

Misdiagnosis and delayed diagnosis for ectopic and heterotopic pregnancies after in vitro fertilization and embryo transfer.

This study examined the misdiagnosis and delayed diagnosis factors for ectopic pregnancy (EP) and heterotopic pregnancy (HP) after in vitro fertilization and embryo transfer (IVF-ET) in an attempt to reduce the diagnostic error. Clinical data of patients who underwent IVF-ET treatment and had clinical pregnancy from 12463 cycles were retrospectively analyzed. Their findings of serum ß-hCG test and transvaginal ultrasonography were also obtained during follow-up. These patients were divided into two groups according to the diagnosis accuracy of EP/HP: early diagnosis and misdiagnosis/delayed diagnosis. The results showed that the incidence of EP and HP was 3.8% (125/3286) and 0.8% (27/3286) respectively for IVF/ICSI-ET cycle, and 3.8% (55/1431) and 0.7% (10/1431) respectively for frozen- thawed embryo transfer (FET) cycle. Ruptured EP occurred in 28 patients due to initial misdiagnosis or delayed diagnosis. Related factors fell in 3 categories: (1) clinician factors: misunderstanding of patients' medical history, insufficient training in ultrasonography and unawareness of EP and HP; (2) patient factors: noncompliance with medical orders and lack of communication with clinicians; (3) complicated conditions of EP: atypical symptoms, delayed elevation of serum ß-hCG level, early rupture of cornual EP, asymptomatic in early gestation and pregnancy of unknown location. All the factors were interwoven, contributing to the occurrence of EP and HP. It was concluded that complicated conditions are more likely to affect the diagnosis accuracy of EP/HP after IVF-ET. Transvaginal ultrasonography should be performed at 5 weeks of gestation. Intensive follow-up including repeated ultrasonography and serial serum ß-hCG tests should be performed in patients with a suspicious diagnosis at admission.

Aberrant DNA methylation of imprinted loci in human spontaneous abortions after assisted reproduction techniques and natural conception.

STUDY QUESTION: Do assisted reproduction techniques (ARTs) affect DNA methylation of imprinted genes and does aberrant methylation of imprinted genes account for the incidence of human spontaneous abortion (SA)? SUMMARY ANSWER: Our results show that imprinting errors of imprinted genes may contribute to human SA, and the occurrence of aberrant methylation of imprinted genes in ART pregnancies was comparable with that in natural pregnancies. WHAT IS KNOWN ALREADY: Animal data and human studies demonstrated that in vitro culture of embryos can cause methylation defects in individual genes, which might affect subsequent embryonic development and contribute to SA. However, our previous studies showed an abnormal methylation pattern of PEG1 in human aborted chrionic villus samples (CVS) but an increased occurrence of aberrant methylation in CVS from ART-derived pregnancies was not observed. STUDY DESIGN, SIZE AND DURATION: CVS were collected from women who underwent abortion procedures in the Department of Gynecology and Obstetrics in Nanfang Hospital from May 2008 to July 2011. Muscle samples (MS) were obtained from aborted fetuses and stillbirths. The samples were divided into four experimental groups: (A) SA/stillbirth after ART (n = 75), (B) multi-fetal reduction after ART (n = 73), (C) SA/stillbirth of natural pregnancies (n = 90) and (D) induced abortion (IA) of natural pregnancies (n = 82). PARTICIPANTS/MATERIALS, SETTING AND METHODS: The mean ± SD age of patients was 31.0 ± 4.1 (range: 18-45 years). The DNA methylation patterns of one paternally methylated (H19) and two maternally methylated (LIT1 and SNRPN) genes were analyzed in CVS and MS using pyrosequencing and bisulfite sequencing PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Clear hypo-methylation (<10%) or hyper-methylation (>90%) were not detected in LIT1 and SNRPN but two regions of hyper-methylation (91.7 and 91.4%) were observed in H19. The mean percentage of methylation in the SA samples (groups A and C) was higher than that in the IA samples (groups B and D; P<0.05). Box plot analyses showed that in the 165 SA samples, methylation values for 40/495 (8.1%) differentially methylated regions of the three genes represented outliers. The incidence of outlier was highest for LIT1 (13.3%, 22/165). In contrast, no outliers were found in the 155 IA samples. The receiver operating characteristic curve analyses showed a positive correlation between percentage methylation of all three genes and incidence of SA (P<0.05). In addition, the conception modes (natural versus ART) and the fertilization methods used in ART (IVF and ICSI) did not affect the methylation patterns of the imprinted genes. No increase in the rate of abnormal methylation was found in the ART samples. LIMITATIONS AND REASONS FOR CAUTION: The studied loci represent only a small fraction of developmentally important genes. Further studies are needed to evaluate changes in the expression and the methylation status of other genes that may lead to SA. WIDER IMPLICATIONS OF THE FINDINGS: The findings provide new insights into the etiology of human SA. The possibility that the abnormal methylation seen is a consequence of the defect that led to the SA cannot be excluded. STUDY FUNDING/COMPETING INTEREST(S): None of the authors has any competing interest. This study was supported by National Natural Science Foundation of China (81170574), The National Key Basic Research Development Plan of China (973 Program) (2007CB948104), Comprehensive strategic sciences cooperation projects of Guangdong Province and Chinese Academy (04020416) and Guangzhou Science and Technology Program key projects (11C22120737).

Minimum dose of hCG to trigger final oocyte maturation and prevent OHSS in a long GnRHa protocol.

This paper was aimed to study the minimum dose of human chorionic gonadotropin (hCG) to effectively trigger maturation of oocytes and prevent ovarian hyperstimulation syndrome (OHSS) in a series of hyper-responders treated with a long gonadotropin releasing hormone agonist (GnRHa) protocol. Six women at high risk of developing severe OHSS in a long GnRHa protocol were enrolled into this study. Serum hormone levels on the day of and after hCG administration, antral follicle count, oocyte retrieval number and quality were determined. In total, 6 women aged between 29 and 36 years and at risk of developing severe OHSS, received 2000 U hCG. Five of them were treated with coasting for 1 day and the rest one for 4 days. The mean number of oocytes collected was 19 (range 14-27) and the fertilization rate per collected oocyte was 72.81%. Of the 6 women in the study, only one cancelled embryos transfer and all embryos were frozen, and then she delivered two health boys on term in the subsequent frozen-thawed embryo transfer (FET) cycle. Pregnancies and births were achieved in 3 patients out of 5 in vitro fertilization-embryo transfer (IVF-ET) cycles. No woman developed moderate or severe OHSS. Triggering with 2000 U hCG is feasible to prevent OHSS in unpredicted hyper-responders undergoing IVF in a long GnRHa protocol.

Cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the bologna criteria.

This study explored the cumulative live birth rate after three ovarian stimulation in vitro fertilization (IVF) cycles for poor ovarian responders according to the Bologna criteria. In this retrospective cohort study, 479 poor ovarian responders according to the Bologna criteria in the first ovarian stimulation IVF cycle between July 2006 and January 2012 in our IVF centre were included. The cumulative live birth rate was calculated by optimistic and pessimistic methods. The cumulative live birth rate after three ovarian stimulation IVF cycles for poor ovarian responders according to the Bologna criteria was 12.7%-20.5%. The three-cycle cumulative live birth rate was 18.5%-24.5%, 13.2%-27.4% and 8.6%-14.9% for poor responders aged ≤35 years, 36-39 years and ≥40 years, respectively. In conclusion, poor responders according to the Bologna criteria can receive an acceptable cumulative live birth rate after three ovarian stimulation IVF cycles, especially poor responders aged <40 years.

Circulating luteinizing hormone level after triggering oocyte maturation with GnRH agonist may predict oocyte yield in flexible GnRH antagonist protocol.

BACKGROUND: The use of gonadotrophin-releasing hormone (GnRH) agonist for triggering final oocyte maturation and ovulation can reduce ovarian hyperstimulation syndrome (OHSS) in high-risk patients. LH levels post-trigger with GnRH agonist might be correlated with oocyte yield and maturity. Our aim was to evaluate the relationship between serum LH level at 12-h post-trigger and oocyte yield, maturity and fertilization rate in patients at high risk of OHSS and therefore who were treated with a flexible GnRH antagonist protocol in which final oocyte maturation was triggered with GnRH agonist. METHODS: In a prospective cohort study, 91 patients at high risk of OHSS were treated with a flexible GnRH antagonist protocol and divided into six groups according to their serum LH levels at 12-h after GnRH agonist administration: ≤15.0, 15.1-30.0, 30.1-45.0, 45.1-60.0, 60.1-75.0 and >75.0 IU/l. The oocyte yield, maturity, fertilization rate and clinical outcomes for each LH interval were analyzed. RESULTS: There was a statistically significant reduction in oocyte yield with a concentration of serum LH ≤15.0 IU/l (P < 0.05), whereas no statistically significant differences in the oocyte maturity and fertilization rate among the six groups (P > 0.05) were seen. Only 5 out of 91 patients (5.5%) had a serum LH ≤15.0 IU/l at 12-h post-trigger with GnRH agonist. In addition, no statistically significant difference was seen regarding high-quality embryos, implantation rate, clinical pregnancy rate and early miscarriage between patients with LH ≤15.0 IU/l and >15.0 IU/l (P > 0.05). CONCLUSIONS: Serum LH level at 12-h post-trigger with GnRHa <15.0 IU/l is associated with a dramatically lower oocyte yield but not with the oocyte maturity and fertilization rate. Serum LH levels post-trigger with GnRH agonist do not affect clinical outcomes.

Embryo retention significantly decreases clinical pregnancy rate and live birth rate: a matched retrospective cohort study.

OBJECTIVE: To investigate the embryo retention (ER) rate in embryo transfer (ET) cycles and its effects on reproductive outcomes. DESIGN: Matched retrospective cohort study. SETTING: A tertiary hospital-based reproductive medicine center. PATIENT(S): A total of 6,089 ET cycles were performed from January 2013 to December 2018 in our unit. INTERVENTION(S): Each woman was matched with two separate control subjects of the same age (±1 year), embryo condition, main causes of infertility, type of protocol used for fresh or frozen ET cycles. MAIN OUTCOME MEASURE(S): ER rate, implantation, clinical pregnancy, ectopic pregnancy, and live birth rate. RESULTS: The overall incidence of ER was 1.59% (97/6,089). A significantly increased ER rate was observed in fresh ET cycles compared with frozen transfer cycles (2.71% vs. 1.08%). In fresh transfer cycles, the rate of mucus in or on the catheter after ET in ER group was significantly higher than in the non-ER group (48.09% vs. 13.65%). A total of 194 non-ER cycles were matched to the ER group. Compared with the matched group, the ER group was associated with a significantly lower clinical pregnancy rate (32.98% vs. 48.96%), implantation rate (20.88% vs. 35.97%), and live birth rate (22.68% vs. 37.63%, P<.01), and a higher ectopic pregnancy rate (12.50% vs. 3.16%). CONCLUSION: Our results suggest that ER rate is correlated with mucus on or in the transfer catheter in fresh transfer cycles. Retained embryos are associated with lower implantation, clinical pregnancy, live birth, and increases risk of ectopic pregnancy.

A Second Dose of GnRHa in Combination with Luteal GnRH Antagonist May Eliminate Ovarian Hyperstimulation Syndrome in Women with ≥30 Follicles Measuring ≥11 mm in Diameter on Trigger Day and/or Pre-trigger Peak Estradiol Exceeding 10 000 pg/mL.

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome (OHSS), characterized by more than 30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL, which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist (GnRHa) trigger and freeze-all policy that previously have been reported. All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards. The in vitro fertilization (IVF) outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS. Moreover, patients' symptoms, reproductive hormone levels and ultrasound findings were improved significantly. This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS, especially for the patients characterized by ≤30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL. Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

[Effect of serum estradiol level before progesterone administration on pregnancy outcomes of frozen-thawed embryo transfer cycles].

OBJECTIVE: To explore whether a high serum estradiol (E2) level before progesterone administration adversely affects the pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles. METHODS: We retrospectively analyzed 205 hormone replacement therapy (HRT)-FET cycles in our Center between February, 2017 and August, 2017. With a cutoff value of serum E2 level of 600 pg/mL before progesterone administration, the cases were divided into high E2 level group and control group with normal E2 level, and the clinical characteristics and pregnancy outcomes were compared between the two groups. RESULTS: No significant difference was found between the two groups in the patients'age during IVF/ICSI cycle, body mass index (BMI) or endometrial thickness at the time of FET (P>0.05). The patients with high E2 levels had a significantly younger age (P<0.05) and a significantly longer duration of estradiol administration than those in the control group (P<0.05). The clinical pregnancy rates, ongoing pregnancy rates, early miscarriage rates, late abortion rates and live birth rates were all comparable between the two groups (P>0.05). After controlling for the compounding factors including the age at FET cycle and the duration of estradiol administration, all these pregnancy outcomes were still comparable between the two groups. CONCLUSION: A high serum E2 level before progesterone administration does not adversely affect the pregnancy outcomes of HRT-FET cycles.

[Successful pregnancy following intracytoplasmic sperm injection?embryo transfer in a patient with premature ovarian insufficiency: a case report].

OBJECTIVE: We report a case of ovarian function fluctuation during long-term follow-up in a patient with premature ovarian insufficiency (POI). The patient finally obtained clinical pregnancy with subsequent uneventful full-term delivery after several intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. This case demonstrates that hormone replacement therapy (HRT) and assisted reproductive therapy should be applied as soon as possible to young patients with POI who have a strong desire for pregnancy in the absence of contraindications. This strategy helps such patients obtain pregnancy and delivery before the exhaustion of ovarian function.

Long Noncoding RNAs: Potential Regulators Involved in the Pathogenesis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age, and its etiology remains poorly understood. Altered activities of long noncoding RNAs (lncRNAs) have been associated with human diseases and development. However, the roles of lncRNAs are unknown in reproductive medicine. We investigated the potential role of lncRNAs in the pathogenesis of PCOS, using human granulosa cells (GCs) and the KGN cell line. We used microarrays to compare lncRNA expression profiles in GCs from seven patients with PCOS and seven matched women. GC samples were collected during 2014 to 2016 from infertile women in Guangzhou, China. Quantitative real-time polymerase chain reaction was used to measure levels of the lncRNA HCG26 in GCs from 53 patients with PCOS and 50 controls. HCG26 was knocked down with locked nucleic acid GapmeRs in KGN cells to examine its role in cell proliferation, aromatase and follicle-stimulating hormone receptor gene expression, and estradiol production. A total of 862 lncRNA transcripts and 998 messenger RNA transcripts were differentially expressed (greater than or equal to twofold change; P < 0.05) in PCOS GCs compared with those of controls. HCG26 levels were upregulated in patients with PCOS and were associated with antral follicle count. HCG26 knockdown in KGN cells inhibited cell proliferation and cell-cycle progression and increased aromatase gene expression and estradiol production. Our study reports the lncRNA profiles in GCs from patients who have PCOS and those from healthy women and suggests that dysregulated lncRNAs may play vital roles in GC proliferation and steroidogenesis, providing insights into the pathogenesis of PCOS.

[Pregnancy outcome in a woman with premature ovarian insufficiency complicated by systemic lupus erythematosus during pregnancy: a case report].

OBJECTIVE: We report a case of in vitro fertilization and embryo transfer (IVF?ET) with oocyte donation in a woman with premature ovarian insufficiency (POI) complicated by systemic lupus erythematosus (SLE) during pregnancy. The patient had a diagnosis of POI 4 years earlier and 11 weeks after successful pregnancy by IVF?ET with oocyte donation in 2003, she presented with facial edema, and further examinations confirmed the diagnosis of lupus nephritis. She received treatment with prednisone to control the activity of SLE and aspirin and low?molecular?weight heparin to improve placental blood flow with close monitoring of gravida and fetus throughout pregnancy. The condition of the patient remained unstable during pregnancy, and liver damage and placental circulation disorder occurred in late gestational weeks with suspected intrauterine growth retardation (IUGR) of the fetus. For maternal and fetal safety, the patient received elective caesarean section and delivered a premature boy at 31 weeks of gestation. She subsequently received further medications for SLE and showed good recovery of the immunological parameters and absence of SLE symptoms during the follow?up for 14 years, indicating a clinical cure of SLE. Her son shows normal growth and development. Based on the experience with this case and literature review, we believe that immunological factor is an important cause of POI and thus recommend full immunological examinations in cases of idiopathic POI.

The association between serum ß-hCG on day 24 of pregnancy and ongoing pregnancy in frozen embryo transfer cycles.

OBJECTIVE: To determine the relationship between serum levels of the ß-subunit of human chorionic gonadotropin (ß-hCG) on day 24 of pregnancy during a frozen embryo transfer (FET) cycle and ongoing pregnancy. METHODS: In a retrospective cohort study, data were reviewed from women aged 38years or younger who underwent a FET cycle at Nanfang Hospital, Guangzhou, China, from January 2013 to December 2014. Inclusion criteria were use of hormone-replacement therapy to achieve an endometrial thickness of 8mm or more, and at least two surviving embryos. Serum ß-hCG on day 24 of pregnancy was assessed in relation to ongoing pregnancy at 12weeks. RESULTS: Overall, 217 patients who underwent 248 FET cycles were included. The only measure that differed between cycles with (n=112) and without (n=136) ongoing pregnancy was ß-hCG level on day 24 of pregnancy (73.0±65.8 vs 19.4±34.5mIU/mL; P<0.001). Classification tree analysis showed that women with day-24 ß-hCG levels higher than 26.6mIU/mL had a 75.8% likelihood of ongoing pregnancy. In receiver operating characteristic curve analysis, the corresponding area under curve was 0.845 (95% confidence interval 0.795-0.895). CONCLUSION: A maternal serum ß-hCG level higher than 26.6mIU/mL was predictive of ongoing pregnancy at 12weeks.

[Outcome analysis of monozygotic twin pregnancy conceived by assisted reproductive techniques].

OBJECTIVE: To analyze the incidence, management, and outcomes of monozygotic twin (MZT) pregnancy conceived by assisted reproductive techniques (ART). METHODS: A retrospective analysis was performed of clinical pregnancies after in vitro fertilization and embryo transfer (IVF-ET) and introcytoplasmic sperm injection and embryo transfer (ICSI-ET) from January, 2010 to June 2015 at our center. We investigated the incidence, managements and outcomes of 94 MZT pregnancies. Comparison of the pregnancy outcomes was made between the expectantly managed MZT pregnancies, dizygotic twin (DZT) pregnancies, monozygotic (MZ)-triplet pregnancies with selective embryo reduction (SER) to 2 fetuses and 1 fetus, and non-MZ triplet pregnancies with SER to 2 fetuses. RESULTS: Ninety-four MZT pregnancies occurred in the total of 6257 clinical pregnancy cycles with an incidence of 1.5%. No significant difference was found in the incidence of MZT pregnancies between IVF and ICSI cycles or between fresh and thawed cycles (P>0.05). Of the 94 MZT pregnancies, 45 were MZT pregnancy cycles, 43 were MZ-triplet pregnancy cycles, 3 were MZ-quadruplet pregnancy cycles and 3 were ectopic pregnancies. The expectantly managed MZT was associated with a significantly greater rate of miscarriage and malformation and a lower rate of live birth and term birth (P<0.05) in comparison with DZT pregnancy cycles that did not undergo SER. Similar outcomes were found between MZ-triplet pregnancies with SER to 2 fetuses and MZ-triplet pregnancies with SER to 1 fetus (P>0.05), and between MZ-triplets with SER to 2 fetuses and non-MZ triplet pregnancies with SER to 2 fetuses (P>0.05). CONCLUSION: ART is associated with a much higher incidence of MZT pregnancies than spontaneous conception. MZT pregnancies are at high risk of adverse outcomes, and reduction of MZT in multiple pregnancies may help to improve the outcomes.

Does lower dose of long-acting triptorelin maintain pituitary suppression and produce good live birth rate in long down-regulation protocol for in-vitro fertilization?

The effects of pituitary suppression with one-third depot of long-acting gonadotropin-releasing hormone (GnRH) agonist in GnRH agonist long protocol for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were investigated. A retrospective cohort study was performed on 3186 cycles undergoing IVF/ICSI with GnRH agonist long protocol in a university-affiliated infertility center. The pituitary was suppressed with depot triptorelin of 1.25 mg or 1.875 mg. There was no significant difference in live birth rate between 1.25 mg triptorelin group and 1.875 mg triptorelin group (41.2% vs. 43.7%). The mean luteinizing hormone (LH) level on follicle-stimulating hormone (FSH) starting day was significantly higher in 1.25 mg triptorelin group. The mean LH level on the day of human chorionic gonadotrophin (hCG) administration was slightly but statistically higher in 1.25 mg triptorelin group. There was no significant difference in the total FSH dose between the two groups. The number of retrieved oocytes was slightly but statistically less in 1.25 mg triptorelin group than in 1.875 mg triptorelin group (12.90±5.82 vs. 13.52±6.97). There was no significant difference in clinical pregnancy rate between the two groups (50.5% vs. 54.5%). It was suggested that one-third depot triptorelin can achieve satisfactory pituitary suppression and produce good live birth rates in a long protocol for IVF/ICSI.

[Clinical outcome of in vitro fertilization or intracytoplasmic sperm injection-embryo transfer in women aged 40 years and above].

OBJECTIVE: To investigate the clinical outcomes in vitro fertilization or intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in women aged over 40 years. METHODS: We retrospectively analyzed 1050 non-donor IVF/ICSI-ET cycles performed from January, 2007 to December, 2015 in women at the age 40 years or above, including 393 women at 40 years of age, 266 at 41 years, 158 at 42 years, 107 at 43 years, 64 at 44 years, and 65 at 45-51 years. The clinical characteristics and outcomes of the women in different age groups were compared and analyzed. The pregnancy outcome of different ovarian stimulation protocols and different numbers of embryo transferred were also compared. RESULTS: Oocyte retrieval was achieved in 1032 treatment cycles. Of the 750 embryo transfer cycles, the clinical pregnancy rate was 17.7% (113/750), and the live birth rate was 8.5% (64/750). The clinical pregnancy rate in the 5 age groups was 23.4%, 21.0%, 13.1%, 9.2%, 5.6% and 0%, and the implantation rate was 11.2%, 10.2%, 6.3%, 5.1%, 2.3% and 0%, respectively; the early spontaneous abortion rate was 31.0%, 35.9%, 42.9%, 42.9% and 100%, and the live birth rate was 11.9%, 11.8%, 2.8% and 3.9%. The clinical pregnancy rates of long protocol, short prorocol, GnRHa antagonist protocol, and ovulation induction protocol were 23.6%, 10.2%, 13.3%, and 2.3%, respectively. In the 750 transfer cycles, the clinical pregnancy rate was 3.8% with single embryo transfer, 12.6% with double embryos transfer, and 23.0% with 3 embryos transfer. CONCLUSION: In women aged 40 years or above, the clinical pregnancy rate decreased significantly with age, and the live birth rate was extremely low in women aged beyond 44 years. Assisted reproductive technique is recommended for women aged 40 years and above even when no identifiable causes of sterility are present. For women aged above 44 years of age, oocyte donation may be a better option.

[Comparison of clinical outcomes of blastocysts derived from non-top quality embryos and cleavage-stage high-quality embryos in frozen-thawed embryo transfer cycles].

OBJECTIVE: To explore the developmental potential of embryos at different developmental days and provide evidence for blastocyst culture of non-top quality cleavage stage embryos in frozen-thawed embryo transfer (FET) cycles. METHODS: The clinical data of 687 FET cycles were retrospectively analyzed. According to the embryo freezing time, the patients were divided into day 5 (D5) blastocyst group (n=87), day 6 (D6) blastocyst group (n=111) and day 3 cleavage-stage embryo (D3) group (n=489) with hormone replacement cycles or natural cycles for endometrial preparation. The clinical pregnancy rates, miscarriage rates, and implantation rates were compared between the 3 groups. RESULTS: The clinical pregnancy rate, miscarriage rate and implantation rate per transfer were 58.6%, 9.8%, and 42.9% in D5 group, 32.4%, 19.4%, and 23.3% in D6 group, and 44.9%, 16.4%, and 26.9% in D3 group, respectively. The clinical pregnancy rate and implantation rate were significantly higher in D5 group than in the other two groups (P<0.05). CONCLUSION: The D5 blastocysts derived from non-top quality D3 embryos after cryopreservation can have better clinical outcomes than those derived from D3 cleavage-stage embryos and D6 blastocysts, and are therefore a better option than D3 cleavage-stage embryos in FET cycles.

Ovarian damage after laparoscopic endometrioma excision might be related to the size of cyst.

OBJECTIVE: To investigate the relationship between the size of an excised endometrioma and the magnitude of damage to the ovary after the surgery. DESIGN: A retrospective, controlled study. SETTING: A university hospital. PATIENT(S): Eighty-five women with a history of laparoscopic excision of unilateral endometrioma who underwent in vitro fertilization (IVF). INTERVENTION(S): IVF-embryo transfer procedures. MAIN OUTCOME MEASURE(S): Antral follicle counts (AFC), number of dominant follicles (follicles ≥ 15 mm), and number of oocytes retrieved. RESULT(S): In the group with cyst diameters of ≥ 4 cm and group with cyst diameters of <4 cm, the AFC, number of dominant follicles, and number of oocytes retrieved were decreased in the operated ovaries when compared with those in intact ovaries; in the former group, a statistically significant reduction was observed. The differences of AFC, number of dominant follicles, and number of oocytes retrieved from both ovaries were further compared among the two groups: the decrease in the group with cyst diameters of ≥ 4 cm was higher than in the group with cyst diameters of <4 cm. After adjusting for age and AFC in intact ovaries, similar results were obtained, although AFC only showed a tendency. In addition, the receiver operating characteristic curve analysis revealed a statistically significant, positive correlation between the size of excised cysts and the incidence of fewer than four oocytes retrieved from an operated ovary. CONCLUSION(S): The magnitude of the ovarian damage after laparoscopic endometrioma excision might be related to the size of cyst; the damage to ovaries is more severe when an endometrioma ≥ 4 cm is excised.