OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).
Infant, Newborn ; Pregnancy ; Female ; Humans ; Fertilization in Vitro/methods* ; Ovarian Reserve ; Prospective Studies ; Premature Birth ; Embryo Transfer/methods* ; Ovulation Induction/methods* ; Gonadotropin-Releasing Hormone/therapeutic use*

OBJECTIVE: To observe the effect of acupuncture on endometrium and pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) infertility undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: Eighty-three patients were randomly assigned to observation group (40 cases) and control group (43 cases) according to the random numbers generated by SPSS software. The patients of the two groups received GnRH agonist long protocol as a routine treatment. In the observation group, acupuncture was given at two acupoint groups for 30 min once every other day. Group 1 included Guanyuan (CV 4), Qihai (CV 6), Zhongji (CV 3), bilateral acupoints Zigong (EX-CA1). Group 2 included Mingmen (GV 4), Yaoyangguan (GV 3), bilateral Shenshu (BL 23) and Ciliao (BL 32). The two groups of acupoints were used alternately. The whole needling process was performed at the time of ovulation induction until the transplantation day and consisted of 3 courses, while the control group did not receive acupuncture interventions. The Gn dosage and Gn stimulation time, endometrial thickness and type (A, B, and C), serum oestradiol (E2) and progesterone (P) levels on the day of injection of human chorionic gonadotropin (hCG), clinical pregnancy rate, as well as live birth rate were observed. Adverse reactions were also be recorded. All patients were followed up for the pregnant rate 14 days after IVF-ET and live birth rate after pregnancy. All adverse reactions (AEs) of acupuncture were recorded during the trial. RESULTS: The Gn dosage and Gn stimulation time in the observation group were lower in the observation group than in the control group (P<0.01). The proportion of type A endometrium in the observation group were higher than that in the control group (P<0.05). The serum E₂ and P levels on the day of hCG injection was lower and the clinical pregnancy rate was higher in the observation group compared to those in the control group (P<0.05). There was no serious AEs during this trial. CONCLUSION Acupuncture can improve the proportion of type A endometrium, regulate the levels of serum E₂ and P on the day of hCG injection, and improve the pregnancy rate in patients with PCOS infertility undergoing IVF-ET.
Acupuncture Therapy/methods* ; Embryo Transfer ; Endometrium ; Female ; Fertilization in Vitro ; Humans ; Infertility ; Ovulation Induction ; Polycystic Ovary Syndrome/therapy* ; Pregnancy ; Pregnancy Outcome

This retrospective study demonstrates the clinical outcomes of patients with nonmosaic Klinefelter's syndrome (KS) who underwent preimplantation genetic testing (PGT) with frozen-thawed testicular spermatozoa. Microdissection testicular sperm extraction (micro-TESE) was performed for sperm retrieval. Next-generation sequencing (NGS) was conducted for embryo analysis. A total of 18 couples aged ≤35 years were included, and 22 oocyte retrieval cycles were completed. Euploidy was detected in 29 of 45 (64.4%) embryos. Additionally, the numbers of aneuploid and mosaic embryos detected were 8 (17.8%) and 8 (17.8%), respectively, regardless of a lack of sex chromosome abnormalities. Finally, 13 couples with euploid embryos completed 14 frozen embryo transfer (FET) cycles. Ten couples had clinical pregnancies, and 6 of them had already delivered 5 healthy babies and 1 monozygotic twin. There were also 4 ongoing pregnancies and 2 biochemical pregnancies, but no early pregnancy loss was reported. Based on our results, we speculate that for KS patients, when sperm can be obtained by micro-TESE, the cryopreservation strategy makes the ovarian stimulation procedure more favorable for female partners. The paternal genetic risk of sex chromosome abnormalities in their offspring is extremely low in men with KS. In addition to PGT, the intracytoplasmic sperm injection (ICSI) procedure is comparably effective but more economical for young nonmosaic KS couples. ICSI should be offered as an option for such couples, but monitoring by prenatal genetic diagnosis is recommended.
Adult ; Female ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Klinefelter Syndrome/therapy* ; Outcome Assessment, Health Care/statistics & numerical data* ; Ovulation Induction/statistics & numerical data* ; Pregnancy ; Retrospective Studies ; Sperm Injections, Intracytoplasmic/methods*

OBJECTIVE: The primary objective of this study was to compare clinical pregnancy rates in intrauterine insemination (IUI) treatment cycles with transabdominal ultrasound guidance during intrauterine catheter insemination (US-IUI) versus the “blind method” IUI without ultrasound guidance (BM-IUI). The secondary objective was to compare whether US-IUI had better patient tolerability and whether US-IUI made the insemination procedure easier for the clinician to perform compared to BM-IUI. METHODS: This was a randomized controlled trial done at the Reproductive Medicine Unit of General Hospital Kuala Lumpur, Malaysia. We included women aged between 25 and 40 years who underwent an IUI treatment cycle with follicle-stimulating hormone injections for controlled ovarian stimulation. RESULTS: A total of 130 patients were recruited for our study. The US-IUI group had 70 patients and the BM-IUI group had 60 patients. The clinical pregnancy rate was 10% in both groups (p> 0.995) and there were no significant difference between the groups for patient tolerability assessed by scores on a pain visual analog scale (p= 0.175) or level of difficulty for the clinician (p> 0.995). The multivariate analysis further showed no significant increase in the clinical pregnancy rate (adjusted odds ratio, 1.07; 95% confidence interval, 0.85–1.34; p= 0.558) in the US-IUI group compared to the BM-IUI group even after adjusting for potential covariates. CONCLUSION: The conventional blind method for intrauterine catheter insemination is recommended for patients undergoing IUI treatment. The use of ultrasound during the insemination procedure increased the need for trained personnel to perform ultrasonography and increased the cost, but added no extra benefits for patients or clinicians.
Catheters ; Female ; Follicle Stimulating Hormone ; Hospitals, General ; Humans ; Insemination ; Insemination, Artificial ; Malaysia ; Methods ; Multivariate Analysis ; Odds Ratio ; Ovulation Induction ; Pain Measurement ; Pregnancy Rate ; Reproductive Medicine ; Ultrasonography ; Visual Analog Scale

OBJECTIVE: To compare laboratory and clinical outcomes of fertilization-embryo transfer (IVF-ET) in patients with endometriosis using antagonist protocol, long agonist protocol or prolonged agonist protocol. METHODS: Totally 313 patients with endometriosis were recruited in Reproductive Centers of the Second Affiliated Hospital of Zhejiang University School of Medicine,Jiaxing Women and Children's Hospital,and Ningbo Women and Children's Hospital from April 2017 to October 2018, including 81 patients treated with antagonist protocol (antagonist group), 148 treated with long agonist protocol (long agonist group) and 84 treated with prolonged agonist protocol (prolonged agonist group). The clinical and laboratory data of the patients were retrospectively analyzed to investigate the effect of ovarian stimulation protocols on the IVF-ET outcomes of patients with endometriosis. RESULTS: The average age in the antagonist group patients was significantly higher than those in the other two groups (all <0.05),and anti-mullerian hormone (AMH) level and antral follicle numbers were significantly lower than those in the other two groups (all <0.01). The numbers of average retrieved oocyte, fertilized oocyte and available embryo in the antagonist group were significantly lower than those in the long agonist group (all <0.05), but were similar with those in the prolonged agonist group (all >0.05). Fertilization rate and available embryo rate were comparable among the three groups (all >0.05). Considering analysis per cycle with embryo transfer, the human chorionic gonadotrophin (HCG) positive rate, clinical pregnancy rate and total implantation rate showed no significant difference among the three groups (all >0.05). The implantation rate after fresh embryo transfer in the antagonist group was lower than that in the long agonist group (<0.05), but was similar with that in the prolonged agonist group (>0.05). While the implantation rate of freeze-thaw embryo transfer showed a higher trend in the antagonist group, but there was no significant difference (>0.05). The patients were further divided into diminished and normal ovarian reserve subgroups, the per cycle with embryo transfer, the HCG positive rate, clinical pregnancy rate and total implantation rate still showed no significant difference between two subgroups (all >0.05), no matter in which ovarian stimulation protocol groups. Besides, in women with diminished ovarian reserve, the available embryo rate in antagonist group was significantly higher than that in the long agonist group (<0.05). The amount and duration of Gn application in antagonist group were significantly lower than those in long and prolonged agonist groups (all <0.05). CONCLUSIONS Patients with endometriosis who used the antagonist protocol in IVF procedure could reduce the cost and time of Gn treatment, when combined with frozen-embryo transfer strategy the antagonist protocol has comparable clinical pregnancy outcome with long or prolonged agonist protocol, especially in those with diminished ovarian reserve, the higher available embryo rate can be achieved.
Embryo Transfer ; Endometriosis ; therapy ; Female ; Fertilization in Vitro ; Humans ; Ovulation Induction ; methods ; Pregnancy ; Retrospective Studies

OBJECTIVE: To investigate prevalence of antiphospholipid antibody (APA) in Korean infertile women undergoing the first in vitro fertilization (IVF) treatment and to evaluate the influence of APA on the subsequent IVF outcomes. METHOD: Two hundred nineteen infertile women who destined the first IVF were prospectively enrolled in 2 infertility centers. Male factor or uterine factor infertility and women with past or current endocrine or immunologic disorders were completely excluded. Plasma concentration of lupus anticoagulant was measured by clot-based method, and anticardiolipin antibody (IgG/IgM), and anti-β2-glycoprotein 1 antibody (IgG/IgM) was measured by enzyme-linked immunosorbent assay method before starting ovarian stimulation for IVF. RESULTS: APA was positive in 13 women (5.9%). Lupus anticoagulant was positive in 2 women (0.9%), anticardiolipin antibody was positive in 7 women (3.2%), and anti-β2-glycoprotein 1 antibody was positive in 4 women (1.8%). In 193 women entering embryo transfer, clinical characteristics and stimulation outcomes were comparable between APA-positive (n=12) and APA-negative group (n=181). The clinical pregnancy rate (66.7% vs. 45.9%), ongoing pregnancy rate (58.3% vs. 37.0%), and miscarriage rate (12.5% vs. 19.3%) were all similar between APA-positive and APA-negative group. CONCLUSION: The prevalence of APA is low in Korean infertile women undergoing the first IVF cycle, and the presence of APA appears to neither decrease their first IVF success nor increase abortion rate.
Abortion, Induced ; Abortion, Spontaneous ; Antibodies, Anticardiolipin ; Antibodies, Antiphospholipid* ; Embryo Transfer ; Enzyme-Linked Immunosorbent Assay ; Female ; Fertilization in Vitro* ; Humans ; In Vitro Techniques* ; Infertility ; Lupus Coagulation Inhibitor ; Male ; Methods ; Ovulation Induction ; Plasma ; Pregnancy ; Pregnancy Rate ; Prevalence ; Prospective Studies

Objective: To analyze the clinical outcomes of repeated superovulation induction in patients with adenomyosis or moderate to severe pelvic endometriosis after failure in previous IVF-ET cycles with the ultra-long protocol. METHODS: We retrospectively analyzed the clinical data about 37 patients with adenomyosis or moderate to severe pelvic endometriosis in our center from 2009 to 2013, who underwent repeated IVF-ET after failure in the previous cycles with the ultra-long protocol, namely by injection of 2－6 ampoules of 3.75 mg gonadotropin-releasing hormone agonist (GnRH-a). All the patients met the following requirements: hCG-negative at 14 days after transfer, within 3－7 days after menstruation, and properly down-regulated serum follicle stimulating hormone (FSH) (<10 mIU/ml), luteinizing hormone (LH) (<10 mIU/ml), estradiol (E2) (<30 pg/ml), follicle diameter (<10 mm) and endometrial thickness, and received GnRH (Gonal-F, Serono) for ovulation induction. We compared the clinical and laboratory data and pregnancy outcomes between the first and repeated cycles before and after ovulation induction. RESULTS: The repeated cycles, as compared with previous ones, showed significant increases in the antral follicle count (AFC) on the first day of stimulation (7.55 ± 1.86 vs 6.45 ± 2.5, P<0.05), number of follicles =≥14 mm in diameter on the hCG trigger day (7.81 ± 3.6 vs 5.56 ± 3.68, P<0.05), level of E2 (［2 362.15 ± 1 210.49］ vs ［1 749.22 ± 1 139.44］ pg/ml, P<0.05), and numbers of oocytes retrieved (7.51 ± 3.23 vs 4.78 ± 3.41, P<0.05) and embryos transferred (2.00 ± 0.33 vs 1.50 ± 0.67, P<0.05), exhibited a remarkably reduction in the dose of GnRH (［1 791.65 ± 1 889.41］ vs ［3 439.56 ± 1 836.53］ IU, P<0.05), and achieved a clinical pregnancy rate of 62.16%. CONCLUSIONS With proper reduction of the FSH, LH and E2 levels and follicle diameter, repeated superovulation induction for IVF-ET can improve the ovarian response and pregnancy outcomes of the patients with adenomyosis or moderate to severe pelvic endometriosis after failure in the previous IVF-ET cycles with the ultra-long protocol.
Endometriosis ; blood ; Estradiol ; blood ; Female ; Fertilization in Vitro ; Follicle Stimulating Hormone ; blood ; Follicle Stimulating Hormone, Human ; blood ; Gonadotropin-Releasing Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Oocytes ; Ovarian Follicle ; Ovary ; Ovulation Induction ; methods ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Recombinant Proteins ; blood ; Retrospective Studies ; Superovulation

As the number of young cancer survivors increases, quality of life after cancer treatment is becoming an ever more important consideration. According to a report from the American Cancer Society, approximately 810,170 women were diagnosed with cancer in 2015 in the United States. Among female cancer survivors, 1 in 250 are of reproductive age. Anticancer therapies can result in infertility or sterility and can have long-term negative effects on bone health, cardiovascular health as a result of reproductive endocrine function. Fertility preservation has been identified by many young patients diagnosed with cancer as second only to survival in terms of importance. The development of fertility preservation technologies aims to help patients diagnosed with cancer to preserve or protect their fertility prior to exposure to chemo- or radiation therapy, thus improving their chances of having a family and enhancing their quality of life as a cancer survivor. Currently, sperm, egg, and embryo banking are standard of care for preserving fertility for reproductive-age cancer patients; ovarian tissue cryopreservation is still considered experimental. Adoption and surrogate may also need to be considered. All patients should receive information about the fertility risks associated with their cancer treatment and the fertility preservation options available in a timely manner, whether or not they decide to ultimately pursue fertility preservation. Because of the ever expanding number of options for treating cancer and preserving fertility, there is now an opportunity to take a precision medicine approach to informing patients about the fertility risks associated with their cancer treatment and the fertility preservation options that are available to them.
Adult Stem Cells ; Cell Culture Techniques ; Cryopreservation/*methods ; *Embryo, Mammalian ; Female ; Fertility Preservation/*methods ; Humans ; Neoplasms/drug therapy/*therapy ; *Oocytes ; Ovarian Follicle/drug effects/metabolism/transplantation ; *Ovary/transplantation ; Ovulation Induction/methods ; Precision Medicine

OBJECTIVETo investigate the factors influencing the pregnancy outcomes of artificial insemination with donor sperm (AID), improve the pregnancy rate, and evaluate the safety of the offspring.

METHODSWe retrospectively analyzed 7,761 cycles of AID for 5,109 infertile couples performed between July 1, 2005 and June 30, 2013 in the Center of Reproductive Medicine of Shenyang No 204 Hospital, the outcomes of pregnancy, and the incidence of birth defects.

RESULTSTotally, 2 252 clinical pregnancies were achieved by AID, in which the pregnancy rate per cycle was 29. 02% and the cumulative pregnancy rate was 44. 08%. The clinical pregnancy rate was remarkably higher in the females of ≤ 35 years than in those of > 35 years old (30.31% vs 20.18%, P < 0.01), in the women with < 5-year infertility than in those with > 5-year infertility (30.83% vs 28.16%, P < 0.01), and in the patients of the ovarian stimulation group than in those of the natural cycle group (33.22% vs 28.68%, P < 0.01) The clinical pregnancy rate was the highest in the first treatment cycle (29.87%), with statistically significant difference from the fourth cycle (23.61%) (P < 0.05), but not between the other cycles (P > 0.05). There were 28 cases of birth defects in the offspring (1.40%), including 6 cases (21.43%) involving the cardiovascular system, 4 (14.29%) involving the musculoskeletal system, 3 (10.71%) involving the urogenital system, 3 (10.71%) involving the central nervous system, 2 cases (7.14%) of cleft lip and palate, 2 (7.14%) involving the respiratory system, 2 (7.14%) involving the gastrointestinal digestive system, and other anomalies.

CONCLUSIONFemale age, infertility duration, and ovarian stimulation treatment are important factors influencing the clinical pregnancy rate of AID. Artificial insemination with cryopreserved donor sperm does not increase the incidence of birth defects, which is considered as a relatively safe technique of assisted reproduction.

Adult ; Cryopreservation ; Female ; Humans ; Infertility ; Insemination, Artificial, Heterologous ; methods ; Male ; Maternal Age ; Ovulation Induction ; Pregnancy ; Pregnancy Outcome ; Pregnancy Rate ; Retrospective Studies ; Semen Preservation ; methods ; Spermatozoa ; Time Factors

Female ; Fertilization in Vitro ; Humans ; Integrative Medicine ; Medicine, Chinese Traditional ; Ovary ; drug effects ; Ovulation Induction ; methods ; Pregnancy ; Pregnancy Rate