Detection of the effect of microvibrational stimulation on human discarded immature oocytes by single-cell transcriptome sequencing technology.

OBJECTIVE: This study aimed to investigate the changes in oocytes at the transcriptome level after applying continuous microvibrational mechanical stimulation to human immature oocytes during in vitro maturation. METHODS: The discarded germinal-vesicle stage (GV) oocytes with no fertilization value after oocytes retrieval in assisted reproduction cycles were collected. Part of them was stimulated with vibration (n = 6) at 10 Hz for 24 h after obtaining informed consent; the other was cultured in static condition (n = 6). Single-cell transcriptome sequencing was used to detect the differences in oocyte transcriptome compared with the static culture group. RESULTS: The applied 10-Hz continuous microvibrational stimulation altered the expression of 352 genes compared with the static culture. Gene Ontology (GO) analysis suggested that the altered genes were mainly enriched with 31 biological processes. The mechanical stimulation upregulated 155 of these genes and downregulated 197 genes. Among them, the genes related to mechanical signaling, such as protein localization to intercellular adhesion (DSP and DLG-5) and cytoskeleton (DSP, FGD6, DNAJC7, KRT16, KLHL1, HSPB1, MAP2K6), were detected. DLG-5, which was related to protein localization to intercellular adhesion, was selected for immunofluorescence experiments based on the transcriptome sequencing results. The protein expression of DLG-5 in the microvibration-stimulated oocytes was higher than that in the static culture oocytes. CONCLUSIONS: Mechanical stimulation affects the transcriptome during oocyte maturation, causing the express changes in intercellular adhesion and cytoskeleton-related genes. We speculate that the mechanical signal may be transmitted to the cell through DLG-5 protein and cytoskeleton-related protein to regulate cellular activities.

[Identification of a novel duplication of Xq13.1 in a case with floppy infant syndrome with SNP-array].

OBJECTIVE: To explore the candidate disease causing gene for a case with floppy infant syndrome (FIS). METHODS: Single nucleotide polymorphism array (SNP array) was used for analyzing the whole genome copy number mutations in the proband. Multiple PCR combined with denaturing high performance liquid chromatography (DHPLC) was employed to verify the suspected mutations in the proband and his family members. RESULTS: A large duplication arr [hg19] Xq13.1: 67 987 646-73 805 828, which spans approximately 5.818182 Mb and encompasses 66 known genes, was identified in the proband. The multiple PCR-DHPLC assay confirmed duplication of HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1 and SLC16A2 genes in the proband. His mother and grandmother both had duplication of the above genes in one X chromosome, but his aunt had not. CONCLUSION: The large Xq13.1 duplication identified by the SNP array probably underlies the FIS in this family. For its high-throughput, high resolution and capacity of automation, SNP array has provided a first line method for the genetic testing for infants featuring developmental delay with unknown reason, mental retardation, autism, multiple malformation and FIS.

The 'normal' range of FMR1 triple CGG repeats may be associated with primary ovarian insufficiency in China.

The aim of this study was to investigate the relationship between normal Fragile X mental retardation gene 1 (FMR1) CGG repeat numbers and primary ovarian insufficiency (POI) occurrence or subsequent resumption of ovarian function. A total of 122 women with POI and 105 controls were followed up and analysed in our centre. The prevalence of premutation and intermediate range of FMR1 CGG repeats in Han Chinese women with POI was only 0.81% (1/122) and 1.64% (2/122), respectively. The risk of POI occurrence for less than 26 CGG repeats and 29 or more CGG repeats in allele1 (smaller allele) was significantly higher than that for 26-28 CGG repeats (odds ratio 13.50, 95% confidence interval: 3.21 to 56.77 and 6.32, 95% confidence interval: 2.49 to 16.09 respectively; both P < 0.001). No significant difference was found in the CGG repeat distribution (<26, 26-28, or ≥29) in FMR1 allele1 between POI cases whose ovarian function resumed and those whose ovarian function did not. It is suggested that the CGG repeat number in allele1, but not that in allele2 (longer allele), was significantly associated with POI occurrence (P < 0.001). Fewer than 26 or more than 28 CGG repeats in FMR1 allele1 were both risk factors of POI occurrence.

Human trophoblast cell during first trimester after IVF-ET differs from natural conceived pregnancy in development and function.

OBJECTIVE: To explore the differences of the trophoblast cell function in first trimester between natural pregnancy and pregnancy after IVF-ET therapy. METHODS: 102 cases with twin to singleton fetal reduction after IVF-ET treatment from July 2010 to August 2013 in Peking University Third Hospital were involved in analysis, and eight specimens were obtained from this group. 10 natural-pregnancy cases undergoing artificial abortion with unwanted pregnancy were recruited as control. Semi-quantitative immunohistochemical method was used to detect the expression of EGFR, Bcl-2, tubulin-α, metallothionein and AFP in villi in both groups. RESULTS: Of the 102 cases, 14 cases (13.73%) were aborted. Preterm birth occurred in seven cases (7.86%). Low birth weight occurred in three patients (3.37%), and extremely low birth weight occurred in four cases (4.49%). The expression of EGFR, tubulin-α, Bcl-2, and metallothionein in the IVF-ET group was significantly lower than that in the control group (P<0.05). However, AFP expression was significantly higher in IVF-ET group than in control group (P<0.05). In IVF-ET group, the miscarriage case had weaker EGFR, tubulin-α, and metallothionein expression than full-term pregnancy; the early preterm labor case had weaker Bcl-2, tubulin-α, and metallothionein expression; and velamentous cord insertion case had weaker tubulin-α expression. CONCLUSIONS: The trophoblast cell function of IVF-ET group in first trimester is different from control group in proliferation, invasion, apoptosis and vascular development, and optimal pregnancy outcome depends on the self-healing balance of trophoblast cells.

Biochemical pregnancy and spontaneous abortion in first IVF cycles are negative predictors for subsequent cycles: an over 10,000 cases cohort study.

PURPOSE: To identify whether biochemical pregnancy (BP) and spontaneous abortion (SA) cases have the same clinical characteristics in assisted reproductive therapy (ART), and to assess its predictive value for the subsequent cycles. METHODS: Retrospectively reviewed 12,174 cycles in the first in vitro fertilization and embryo transfer (IVF-ET) cycle from January 2009 to December 2012 of Peking University Third Hospital Reproductive Medical Center. Besides those patients who reached ongoing pregnancy stage, 7,598 cases were divided into three groups: group 1, lack of pregnancy (n = 6,651); group 2, BP (n = 520); and group 3, SA (n = 427). We compared the basic status of patients of the three groups, including ages, body mass index, basic hormone levels, controlled ovarian hyperstimulation protocols, amount of gonadotropin use, and endometrium thickness. The reproductive outcome of the next embryo transfer cycles of the three groups was analyzed. RESULTS: 520 patients ended as BP, and 427 patients ended as SA. The age, primary infertility proportion, body mass index, basic FSH level and basic E2 level were similar among groups. Endometrial thickness, controlled ovarian hyperstimulation protocol, Gn dosage, average oocyte retrieval and ET numbers were also similar. Multivariate analysis showed that only the age (P = 0.037, OR 1.060, 95 % CI 1.001-1.120) and endometrium thickness on hCG administration day (P = 0.029, OR 1.136, 95 % CI 1.013-1.275) may result in the differences between BP and SA groups. In the subsequent ET cycles, the total BP rate was 4.37 %, clinical pregnancy rate was 37.28 %, and miscarriage rate was 8.18 %. The clinical pregnancy rates were similar among groups. However, BP group still had the highest BP rate (P < 0.05, 7.97 vs. 4.01 % and 5.28 %), BP and SA group had higher miscarriage rate (P < 0.05, 11.76 % and 14.75 vs. 7.41 %). CONCLUSION: BP and SA in first IVF cycles had negative predictive value for subsequent ART outcomes.

The individualized choice of embryo transfer timing for patients with elevated serum progesterone level on the HCG day in IVF/ICSI cycles: a prospective randomized clinical study.

This study analyzed the clinical outcomes of patients with elevated progesterone level on the HCG day in IVF/ICSI cycles, with different timing of embryo transfer. A total of 123 patients were involved in this prospective randomized clinical study. Group 1: blastocyst transfer group, 38 cases; Group 2: frozen-thawed embryo transfer group (first FET cycle), 42 cases; Group 3: fresh embryo transfer group, 43 cases. The basal FSH level was comparable among three groups (6.7 ± 3 versus 7.0 ± 2 versus 6.9 ± 2.4, p = 0.897). The clinical pregnancy rate was highest in group 2, lowest in group 3, with significantly difference (31.6% versus 38.1% versus 13.9%, p = 0.037). The implantation rate and live birth rate were still lowest in group 3 (21.9% versus 19.8% versus 6.7%, p = 0.016 and 18.4% versus 31% versus 11.6%, p = 0.081). In conclusion, the elevated progesterone level will affect clinical pregnancy rate in fresh embryo transfer cycles. We suggest frozen-thawed embryo transfer for these patients. However, for those patients who expressed the wish to have fresh embryo transfer, they should be suggested fresh blastocyst transfer, if they have more than five good quality embryos.

The Prognosis of IVF in Poor Responders Depending on the Bologna Criteria: A Large Sample Retrospective Study from China.

OBJECTIVE: To analyze the treatment outcomes of patients who accepted IVF/ICSI-ET, diagnosed POR according to Bologna criteria. STUDY DESIGN: Retrospective cohort study of one reproductive medical center, from 1st Jan., 2009, to 31st Dec., 2014. All patients fulfilled the Bologna criteria and accept IVF/ICSI-ET treatment with stimulation cycle. The main outcome measures were clinical pregnancy rate (CPR) and live birth rate (LBR). RESULTS: There were 5770 eligible cycles included in this study. The incidence of POR was 10.3% (6286/62194). The overall CPR was 18.7%, IR was 11.6%, LBR/ET was 11.5%, and LBR/OPU was 8.3%. The cycle cancellation for no available oocyte or embryo was 4.9% and 18.6%, respectively. The subgroup of younger POR patients got highest CPR and LBR/ET, which decreased while increasing maternal age. Within three attempts, the patients got similar CPR and LBR. CONCLUSION: In conclusion, our study supports the Bologna criteria that defined women with poor IVF outcomes. But those younger than 42 years old with the first 3 attempts of IVF could got acceptable CPR and LBR.

[Influence of duration of gonadotropin administration on the clinical outcome of in vitro fertilization embryo transfer].

OBJECTIVE: To investigate the influence of duration of gonadotropin (Gn) administration on the clinical outcome of in vitro fertilization embryo transfer (IVF-ET). METHODS: A total of 3 221 cycles of short protocol or antagonist protocol in our center from January 2012 to December 2012 were included in the retrospective study. According to the different duration of Gn administration, all patients were divided into group A (≤7 days, n=58) and group B (>7 days, n=3 163). The different clinical parameters, such as age, duration of infertility, body mass index (BMI), basis estradiol (E2), follicle-stimulating hormone (FSH), the number of antral follicle, the number of oocytes, endometrium thickness, fertility rate, good quality embryo rate, impatation rate and clinical pregnancy rate were compared between the two groups. RESULTS: There was no significant difference in age, duration of infertility, BMI, basis E2, FSH, the number of antral follicle between the two groups. The number of oocytes in group A was fewer than that in group B [(8.2±5.6)vs.(12.1±8.3), P=0.009]; endometrium thickness on the day of HCG in group A was thinner than that in group B [(9.9±2.1) mm vs.(10.4±1.6) mm,P=0.002]. There was no significant difference in fertility rate, good quality embryo rate, impatation rate and clinical pregnancy rate (36.2% vs. 33.6%, P>0.05). There was no significant difference in clinical pregnancy rate between the two groups in short protocol (33.3% vs. 27.2%, P>0.05). In the same way, there was no significant difference in clinical pregnancy rate between the two groups in antagonist protocol (37.5% vs. 36.6%, P> 0.05). CONCLUSION: Although short duration of gonadotropin administration in short protocol and antagonist protocol has association with fewer number of oocytes, it may not affect the outcome of IVF-ET.

[Comparison of gonadotropin releasing hormone agonist long protocol and gonadotropin releasing hormone antagonist protocol in infertile women].

OBJECTIVE: To compare the clinical outcomes of GnRH agonist (GnRH-a) long protocol and GnRH antagonist (GnRH-ant)protocol in vitro fertilization (IVF)-embryo transfer (ET) cycles, and to explore the optimized protocol for infertile women. METHODS: From June 2010 to June 2012, 2 444 infertile women underwent their IVF cycles in Peking University Third Hospital, which were divided into 1 706 GnRH agonist long protocol and 738 GnRH antagnist protocol groups. The data of the general demographic, treatment and clinical outcome were compared between the two groups. RESULTS: The age, body mass index(BMI), infertile duration, antral follicle count (AFC) did not reach statistical difference, the level of estradiol on the day of HCG: injection was higher in GnRH agonist group [(10 595±7 368)pmol/L vs. (9 087±7 035) pmol/L], and the mean length of stimulation was longer in GnRH agonist group[(12.5±1.8) d vs.(9.4±1.7) d], The dose of Gn [(3 107±1 377) IU vs. (2 084±903)IU]was higher in GnRH agonist group. The number of ovum was 13.4±6.6 in GnRH agonist group and 11.8±6.4 in GnRH antagonist group. Those clinical parameters all reached statistical difference (P<0.05). The number of the transfer embryos, fertilization rate, and cleavage rate did not reach statistical difference, but the number of the embryos was 5.6±4.5 in GnRH agonist group and 5.1±4.3 in GnRH antagonist group,reached statistical difference (P<0.05). The abortion rate, embryonic death rate, ectopic pregnancy rate, preterm labor rate, postterm pregnancy rate, fatal malformations rate showed no statistical difference, but the GnRH agonist long protocol had higher pregnancy rate (44.0% vs. 38.3%), and higher term pregnancy rate (64.2% vs. 56.9%) compared with GnRH antagonist protocol, thus those parameter reached significant difference (P<0.05). CONCLUSION: Compared with GnRH-antagnist protocol, GnRH agonist long protocol had higher pregnancy rate and better pregnancy outcome.

[Analysis of clinical factors affecting pregnancy rate of intrauterine insemination].

OBJECTIVE: To analyze the factors affecting clinical pregnancy rate of intrauterine insemination in Center of Reproductive Medicine, Peking University Third Hospital, to guide clinical treatment. METHODS: In the study, 5 167 intrauterine insemination cycles were retrospectively analyzed from May 2011 to October 2012 in our reproductive center. The data were collected, the single-factor was analyzed with χ2 test, and the multi-factor was analyzed with Logistic regression with a significant level of 0.05. RESULTS: The cycle clinical pregnancy rate was 12.8%, which decreased with the increase of the female age and infertile duration. The clinical pregnancy rate was low when the sperm density was less than 1×10(6)/mL. In the ovulation group, the clinical pregnancy rate was higher than the natural group. The group with more than 2 dominant follicles had higher clinical pregnancy rate as compared with the single dominant follicle group. The clinical pregnancy rate was the highest in the third cycle but decreased after the fourth cycle. The clinical pregnancy rate was higher in cervical factors, sexual dysfunction, and polycystic ovary than in the group with other reasons. CONCLUSION: The female age, infertile duration, ovarian stimulation and follicle number, cause of infertility were the main factors affecting clinical pregnancy outcome; the sperm density, and cycle numbers have influence too; the insemination timing, and frequency have little effect.

Intracranial KCl injection--an alternative method for multifetal pregnancy reduction in the early second trimester.

OBJECTIVE: This study aimed to assess the effectiveness and feasibility of transabdominal intracranial KCl injection as an alternative to intrathoracic KCl injection for multifetal pregnancy reduction (MFPR) in the early second trimester. METHODS: In this study, 40 cases who underwent fetal reduction between 12 and 18 weeks of gestation at the Reproductive Medical Center of Peking University Third Hospital from January 2006 to December 2011 were divided into two groups: group A (16 cases of intracranial injection) and group B (24 cases of intrathoracic injection). The groups were compared for clinical procedures and outcomes. RESULTS: The two groups were similar in terms of patient age, gestation, as well as starting and finishing fetal numbers. Group A needed significantly fewer punctures for each fetus than group B did (1.1 ± 0.2 vs. 1.4 ± 0.6), but both groups received similar doses of KCl (2.6 ± 0.8 ml vs. 2.6 ± 1.2 ml per fetus). All cases succeeded in the first procedure, with no heartbeat recovery. The two groups had similar miscarriage rates and gestational ages at delivery. CONCLUSION: MFPR by intracranial KCl injection was as effective as, but an easier procedure than intrathoracic KCl injection between 12 and 18 weeks of gestation.

Retain singleton or twins? Multifetal pregnancy reduction strategies in triplet pregnancies with monochorionic twins.

OBJECTIVE: To assess the effectiveness and feasibility of retaining a singleton or twins for multifetal pregnancy reduction (MFPR) in triplet pregnancy with monochorionic twins. STUDY DESIGN: This retrospective study was conducted from January 2006 to September 2011 at a university reproductive medical center. Multifetal pregnant patients (n=35) with dichorionic triplets underwent MFPR in the first trimester to reduce one or both monochorionic twins. These cases were divided into two groups: Group A (9 MFPR cases to reduce one monochorionic twin) and Group B (26 MFPR for both monochorionic twins). Control A (for Group A) included another 18 cases of trichorionic triplet reduction to twins; Control B (for Group B) included 35 cases of trichorionic triplet reduction to singletons. MFPR was performed during the same period for all groups. Pregnancy outcomes were compared between groups. RESULTS: Patients were 28-39 years old; the average gestation for fetal reduction was 6-8 weeks. The early abortion rate was lower in Group A than Group B (0 versus 11.5%, p=0.339), but the late abortion rate was significantly higher in Group A. (33.3% versus 0, p=0.000). Groups A and B did not differ significantly in premature labor rate, term birth rate, gestation at delivery and take-home baby rate. The rate of very low and low birth weight was significantly higher in Group A than Group B (50% versus 0, p=0.001), and the average birth weight was significantly lower in Group A (2391.7±318.5 versus 3119.6±523.9, p=0.001). Group A had significantly more low birth-weight newborns than Control A (50% versus 13.3%, p<0.05 [0.024]). Group B (retained singleton) had similar pregnancy outcomes and neonatal conditions as Control B. CONCLUSIONS: Retaining a singleton is always the best choice when deciding about using MFPR to improve pregnancy outcomes. For patients having a triplet pregnancy with monochorionic twins and strongly desiring to keep twins, MFPR in one monochorionic twin was feasible by aspirating embryonic parts early in gestation (6-8 weeks) with no drug injection. Pregnancy outcomes are similar with twin reduction in trichorionic triplet pregnancy.

[Comparison of GnRH antagonist fixed protocol and GnRH agonists long protocol in infertile patients with normal ovarian reserve function in their first in vitro fertilization-embryo transfer cycle].

OBJECTIVE: To compare the clinical outcomes of gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) fixed protocol with GnRH agonist (GnRH-a) long protocol in infertile patients with normal ovarian reserve function in their first in vitro fertilization-embryo transfer (IVF-ET) cycle, and to explore the feasibility and advantage of GnRH antagonist protocol performed in normal responders. METHODS: From January 2011 to June 2011, 771 infertile women with normal ovarian reserve function underwent their first IVF or intracytoplasmic sperm injection (ICSI) cycles in Peking University Third Hospital, which were divided into 245 cycles in GnRH-ant fixed protocol group (GnRH-ant group) and 526 cycles in GnRH-a long protocol group (GnRH-a group). The data of general demographic, treatment and clinical outcome were compared between two groups. RESULTS: Age, infertile duration, body mass index (BMI), baseline serum follicle-stimulating hormone (FSH) and estradiol levels between two groups did not reached statistical difference (P > 0.05). The level of estradiol was (12 289 ± 6856) pmol/L in GnRH-ant group and (14 934 ± 8007) pmol/L in GnRH-a group at day of hCG injection. The mean length of stimulation was (10.3 ± 1.2) days in GnRH-ant group and (12.8 ± 1.6) days in GnRH-a group. The dose of gonadotropin was (2013 ± 607) U in GnRH-ant group and (2646 ± 913) U in GnRH-a group. The number of ovum was 15 ± 7 in GnRH-ant group and 17 ± 8 in GnRh-a group. Those clinical parameter all reached statistical difference (P < 0.05). The number of embryo was 7 ± 4 in GnRH-ant group and 8 ± 5 in GnRH-a group, the rate of clinical pregnancy was 40.9% (94/230) in GnRH-ant group and 45.6% (216/474) in GnRH-a group, the rate of implantation was 26.1% (128/490) in GnRH-ant group and 30.9% (307/994) in GnRH-a group, the rate of continuing pregnancy was 38.7% (89/230) in GnRH-ant group and 42.6% (202/474)in GnRH-a group, those parameter did not reach statistical difference (P > 0.05). The rate of moderate or severe ovarian hyperstimulation syndrome was 2.4% (6/245) in GnRH-ant group and 4.2% (22/526) in GnRH-a group, which did not show significant difference (P > 0.05). CONCLUSION: In the first IVF or ICSI cycle of the patients with normal ovarian reserve function, the fixed GnRH-ant protocol could get the same satisfied clinical outcome, and it is more economic, convenient and safer compared with low dose depot GnRH-a long protocol.

Efficacy of local aspiration in the conservative treatment of live interstitial pregnancy coexisting with live intrauterine pregnancy after in vitro fertilization and embryo transfer.

BACKGROUND: Heterotopic pregnancy (HP) is defined as a pregnancy in which one or more embryos is viably implanted in the uterus while the other is implanted elsewhere as an ectopic pregnancy. The occurrence of HP rises dramatically with the increased use of assisted reproductive technology. HP of interstitial pregnancy is one special situation which needs more concern. Here we evaluate the efficacy of local aspiration and instillation of hyperosmolar glucose in the treatment of live interstitial pregnancy complicated with live intrauterine pregnancy after in vitro fertilization and embryo transfer. METHODS: Five female patients were diagnosed with live interstitial pregnancies complicated with intrauterine pregnancies. They were treated with transvaginal ultrasound-guided aspiration of interstitial pregnancy and instillation of hyperosmolar glucose at the Center for Reproductive Medicine of Peking University Third Hospital from January 1st, 2008 to May 30th, 2011. RESULTS: Gemmule embryos in all 5 cases were aspirated successfully and there was no abdominal hemorrhage, threatened abortion or infection in any of the cases. The sac of interstitial pregnancy continued to progress after aspiration and stopped growing between 11 to 20 weeks. By the 30th week of pregnancy, 80% of the interstitial masses had disappeared. Four cases have delivered and one is still in on-going pregnancy. All of the four cases underwent cesarean section and there were nothing special detected in the corner of the uterus. CONCLUSION: Local aspiration and instillation of hyperosmolar glucose may be an effective way to treat live interstitial pregnancy when coexisting with a live intrauterine pregnancy.

Effect of HCG-day serum progesterone and oestradiol concentrations on pregnancy outcomes in GnRH agonist cycles.

This study analysed the relationship between serum progesterone/oestradiol concentrations and IVF pregnancy outcomes in gonadotrophin-releasing hormone agonist protocols. A total of 2921 infertile women undergoing IVF were assigned to four groups according to serum progesterone and oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration: group 1 (control) progesterone<3.34 nmol/l and oestradiol<19,124 pmol/l; group 2 (high oestradiol); group 3 (high progesterone); group 4 (high progesterone and high oestradiol). Compared with group 1, group 4 had lower clinical pregnancy and live birth rates as well as the highest ectopic pregnancy rate (29.15% versus 45.91%; 18.67% versus 34.34%; 18.10% versus 5.82%; P<0.05). Group 3 had lower clinical pregnancy and live birth rates per embryo-transfer cycle (29.78% versus 45.91%; 20.28% versus 34.34%, respectively; P<0.05). Clinical pregnancy rates were similar in frozen-thawed embryo transfers (FET) among the four groups. In conclusion, elevated progesterone was detrimental to live birth rates. High serum oestradiol concentration on HCG day did not affect the IVF pregnancy outcome. In combination with the elevated progesterone, high oestradiol concentrations had a potential negative effect. For these patients, FET should be suggested to improve the pregnancy outcomes. The aim of this study was to analyse the relationship between serum progesterone/oestradiol concentrations and IVF pregnancy outcomes in gonadotrophin-releasing hormone agonist protocols. A total of 2921 infertile women undergoing IVF were assigned to four groups according to their serum progesterone and oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration: group 1 (control) progesterone<3.34 nmol/l and oestradiol<19,124 pmol/l; group 2 (high oestradiol); group 3 (high progesterone); group 4 (high progesterone and high oestradiol). Compared with group 1, patients in group 4 had lower clinical pregnancy (29.15% versus 45.91%) and live birth rates (18.67% versus 34.34%) as well as the highest ectopic pregnancy rate (18.1% versus 5.82%) (all P<0.05). Those in group 3 had lower clinical pregnancy and live birth rates per embryo transfer cycle (29.78% versus 45.91%; 20.28% versus 34.34%, respectively, P<0.05). Embryo quality appeared to be unaffected since similar clinical pregnancy rates in frozen-thawed embryo transfer (FET) cycles among the four groups. In conclusion, elevated progesterone was detrimental to live birth rates. A high serum oestradiol concentration on the day of HCG administration did not affect the IVF pregnancy outcome. In combination with the elevated progesterone and oestradiol concentrations had a potential negative effect. For these patients, FET should be suggested to improve the pregnancy outcomes.

The usefulness of transvaginal hydrolaparoscopy in infertile women with abnormal hysterosalpingogram results but with no obvious pelvic pathology.

OBJECTIVE: To evaluate the value of transvaginal hydrolaparoscopy (THL) in infertile women with abnormal hysterosalpingogram results but with no history of previous pelvic surgery and with normal gynecological examination and vaginal sonography. STUDY DESIGN: This is a retrospective study. From January 2008 to October 2009, 51 infertile women were planned to undergo standard laparoscopy because of abnormal HSG. None of the patients had any history of previous pelvic surgery and all had normal findings on gynecological examination and vaginal sonography. These women underwent THL. RESULTS: Among the 51 cases, successful access to the pouch of Douglas was achieved in 49. There were two failures due to obesity, and the operation was converted to standard laparoscopy. No complication was observed in this study period. In 26 patients (53.1%) the THL procedure showed normal pelvic organs. Four patients were lost to follow-up. Of the remaining 22 cases, four became pregnant (4/22, 18.2%) through intercourse or intrauterine insemination (IUI). There were some morphologic abnormalities seen in the remaining 23 patients such as adhesions, endometriosis and hydrosalpinx. Six cases with mild adhesions and endometriosis were treated with THL alone, and four (4/6, 66.7%) became pregnant with or without IUI. Among the 19 who underwent standard laparoscopy, three were lost to follow-up. In the other 16 cases, natural pregnancy occurred in six (6/16, 37.5%) patients with or without IUI. CONCLUSIONS: For women with abnormal HSG results but with no obvious pelvic pathology, THL should be recommended and about 50% could avoid an unnecessary laparoscopy. Adhesiolysis and coagulation of endometriotic lesions under THL in mild adhesion and endometriosis cases could lead to encouraging results.

Comparison of the major malformation rate of children conceived from cryopreserved embryos and fresh embryos.

BACKGROUND: Cryopreserved embryo transfer has become indispensable in reproductive technology. More and more children are conceived from frozen-thawed embryo transfer (FET). The risk of birth defects associated with frozen-thawed embryo transfer has been evaluated and conflict results are obtained. The aim of this study was to compare the rate of major malformations in children conceived from cryopreserved embryos with that of children from fresh embryos. METHODS: A retrospective analysis was performed on children conceived from frozen-thawed embryos and fresh embryos between January 2005 and December 2008 at the Reproduction Center of the Third Hospital, Peking University. The major malformation rates were compared between two groups for all children, as well as singletons or twins, separately. The frequencies of different subtypes of malformations classified according to different organ system were also compared. RESULTS: Thirty-four of 3125 children from cryopreserved embryos had a major malformation. The malformation rate was 1.09%, which was comparable to that for children after fresh embryos transfer (1.53% (55/3604), OR: 0.71, 95%CI; 0.46-1.09). The malformation rate was also similar when the analysis was limited to children from cryopreserved embryos resulted from in vitro fertilization (IVF) (1.39%) and fresh IVF (1.3%). However, children from cryopreserved embryos resulted from intracytoplasmic sperm injections (ICSI) had much lower malformation rate than from fresh ICSI (0.63% vs.1.83%, OR: 0.34, 95%CI: 0.16-0.75). No difference was found in the incidence of major malformations in singletons from cryo ICSI (0.73%) and fresh ICSI (1.9%), or from cryo IVF (1.49%) and fresh IVF (1.67%). Similar malformation rate was found in multiples from cryo ICSI (0.52%) and fresh ICSI (1.76%), or cryo IVF (1.30%) and fresh IVF (0.90%). The distribution and risk of the subtype of malformations, such as cardiovascular, gastrointestinal, neural tube, urogenital, musculoskeletal and facial abnormalities was not different between the cryo group and fresh group. CONCLUSIONS: The major malformation rate is similar between fetuses/children conceived from cryopreserved embryos and those from fresh embryos. Large prospective and long-term follow-up studies are needed to get exact results concerning the birth defects of the children born after cryopreserved embryos.

The role of family history in clinical symptoms and therapeutic outcomes of women with polycystic ovary syndrome.

OBJECTIVE: To investigate the association between family history and clinical symptoms of polycystic ovary syndrome (PCOS) that were thought to be inherited, by treating women with PCOS with contraceptive pills and metformin, and assessing outcomes. METHODS: Of 164 women with PCOS, 49 with menstrual abnormalities, hyperandrogenism, and abnormal glucose and/or insulin levels underwent a 3-month treatment with contraceptive pills and metformin. Family history was taken, and physical and ultrasound examinations were performed. Serum levels of glucose, insulin, lipoproteins, lipids, and reproductive hormones were measured before and after treatment. RESULTS: The serum levels of low-density lipoprotein, total cholesterol, apolipoprotein B, and triglycerides were higher in the patients with a family history of the studied symptoms than in those with no such family history. After treatment, changes in testosterone and glucose levels, glucose area under curve, and homeostasis model assessment value differed in the 2 groups. CONCLUSION: The patients with a family history of PCOS symptoms thought to be inherited were more sensitive to oral contraceptive and metformin treatment.

[Effect of hyperprolactinemia upon clinical symptoms of patients with polycystic ovary syndrome].

OBJECTIVE: To determine the effects of hyperprolactinemia (hyperPRL) upon the symptoms of patients with polycystic ovary syndrome (PCOS). METHODS: Age, body mass index, levels of hormone, lipid, beta-cell function and family medical history of 224 women with PCOS and 30 women with hyperPRL + PCOS were compared. RESULTS: Patients with hyperPRL + PCOS were younger to develop endocrine disturbances, an increased incidence of acne (64% vs 28% respectively), a high level of androstenedione (20 + or - 7 vs 13 + or - 5) nmol/L respectively and prolactine in serum (1492 + or - 1175 vs 367 + or - 164) mIU/L respectively; The PCOS patients were divided into the groups of hyperandrogenism PCOS and non-hyperandrogenism PCOS depending on the serum level of androgen. A higher level of T and A was found in serum in PRL-PCOS than non-hyperandrogenism patients and similar as hyperandrogenism PCOS patients. They had reduced ApoB (680 + or - 230 nmol/L vs 943 + or - 179 mmol/L respectively) and Lpa level (46 + or - 22 nmol/L vs 162 + or - 194 mmol/L respectively) and high HOMA-IR when compared with non-hyperandrogenism PCOS; Patients' sisters with hyperPRL + PCOS had a significantly greater incidence of acne, higher rates of infertility and PCOS when compared with PCOS patients. Levels of other hormones, metabolic profiles and other family histories did not differ between patients with PCOS and hyper-PRL+PCOS. CONCLUSION: Patients with hyperPRL + PCOS develop the endocrine disturbances at a younger age, a greater incidence rate of acne, level of prolactin and androstenedione, they have reduced ApoB and increased HOMA-IR. Patients' sisters with hyperPRL + PCOS have significantly greater incidence of acne, higher rates of infertility and PCOS as when compared with PCOS patients.