Qiuju Chen

Luteal-phase ovarian stimulation is feasible for producing competent oocytes in women undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, with optimal pregnancy outcomes in frozen-thawed embryo transfer cycles.

OBJECTIVE To explore the feasibility of luteal-phase ovarian stimulation using hMG and letrozole in terms of ovarian response and pregnancy outcome using frozen-thawed embryo transfer. DESIGN A prospective cohort study. SETTING Academic tertiary-care medical center. PATIENT(S) Two hundred forty-two female patients undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. INTERVENTION(S) Ovarian stimulation was initiated with hMG 225 IU and letrozole 2.5 mg daily after spontaneous ovulation. Letrozole administration was stopped when the dominant follicles reached diameters of 12 mm. Ovulation was induced with a GnRH agonist 100 μg when at least three follicles reached diameters of 18 mm or one dominant follicle reached 20 mm. The highest quality embryos were extracted and cryopreserved for later transfer. MAIN OUTCOME MEASURE(S) The primary outcome measured was the number of oocytes retrieved. Secondary outcomes were the clinical pregnancy rate, ongoing pregnancy rate, and implantation rate after frozen embryo transfer (FET) cycles. RESULT(S) Of the 242 women enrolled in the study, all participants succeeded in producing oocytes and 227 women had highest-quality embryos to cryopreserve. The average number of oocytes retrieved was 13.1, producing an average of 4.8 highest quality embryos. Moreover, no cases experienced a premature LH surge or moderate/severe ovarian hyperstimulation syndrome during the stimulation cycles. In FETs, the clinical pregnancy rate, ongoing pregnancy rate, and implantation rate were 55.46% (127/229), 48.91% (112/229), and 40.37% (174/431), respectively. Of all the pregnancies in the study, 68 resulted in live births and 44 were ongoing. CONCLUSION(S) Luteal-phase ovarian stimulation is feasible for producing competent oocytes/embryos in women undergoing IVF/ICSI treatments, with optimal pregnancy outcomes in FET cycles.

Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol)

Previous studies have shown that existing antral follicles in the luteal phase enable ovarian stimulation. In a pilot study, the efficacy of double stimulations during the follicular and luteal phases in women with poor ovarian response was explored (defined according to the Bologna criteria). Thirty-eight women began with mild ovarian stimulation. After the first oocyte retrieval, human menopausal gonadotrophin and letrozole were administrated to stimulate follicle development, and oocyte retrieval was carried out a second time when dominant follicles had matured. The primary outcome measured was the number of oocytes retrieved: stage one 1.7 ± 1.0; stage two 3.5 ± 3.2. From the double stimulation, 167 oocytes were collected and 26 out of 38 (68.4%) succeeded in producing one to six viable embryos cryopreserved for later transfer. Twenty-one women underwent 23 cryopreserved embryo transfers, resulting in 13 clinical pregnancies. The study shows that double ovarian stimulations in the same menstrual cycle provide more opportunities for retrieving oocytes in poor responders. The stimulation can start in the luteal phase resulting in retrieval of more oocytes in a short period of time. This offers new hope for women with poor ovarian response and newly diagnosed cancer patients needing fertility preservation.

Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization

OBJECTIVE To investigate the use of medroxyprogesterone acetate (MPA) to prevent LH surge during controlled ovarian hyperstimulation (COH) and to compare cycle characteristics and pregnancy outcomes in subsequently frozen-thawed ET (FET) cycles. DESIGN A prospective controlled study. SETTING Tertiary-care academic medical center. PATIENT(S) Three hundred patients undergoing IVF/intracytoplasmic sperm injection treatment. INTERVENTION(S) In the study group, hMG and MPA were administered simultaneously beginning on cycle day 3. Ovulation was induced with a GnRH agonist or cotriggered by a GnRH agonist and hCG when dominant follicles matured. A short protocol was used in the control group. Viable embryos were cryopreserved for later transfer in both protocols. MAIN OUTCOME MEASURE(S) The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the number of mature oocytes, the incidence of premature LH surge, and clinical pregnancy outcomes from FETs. RESULT(S) The number of oocytes retrieved in the study group was similar to those in the controls (9.9 ± 6.7 vs. 9.0 ± 6.0), and higher doses of hMG were administered. In the study group, LH suppression persisted during ovarian stimulation, and the incidence of premature LH surge was 0.7% (1/150). No statistically significant differences were found in the clinical pregnancy rates (47.8% vs. 43.3%), implantation rates (31.9% vs. 27.7%), and live-birth rates (42.6% vs. 35.5%) in the study group and controls. CONCLUSION(S) The results show that MPA is an effective oral alternative for the prevention of premature LH surge in woman undergoing COH. This finding will help establish a new regimen for ovarian stimulation in combination with embryo cryopreservation. CLINICAL TRIAL REGISTRATION NUMBER ChiCTR-ONRC-14004419.

Comparison of live-birth defects after luteal-phase ovarian stimulation vs. conventional ovarian stimulation for in vitro fertilization and vitrified embryo transfer cycles

OBJECTIVE To assess live-birth defects after a luteal-phase ovarian-stimulation regimen (LPS) for in vitro fertilization (IVF) and vitrified embryo transfer (ET) cycles. DESIGN Retrospective cohort study. SETTING Tertiary-care academic medical center. PATIENT(S) Infants who were born between January 1, 2013 and May 1, 2014 from IVF with intracytoplasmic sperm injection (ICSI) treatments (n = 2,060) after either LPS (n = 587), the standard gonadotropin-releasing hormone-agonist (GnRH-a) short protocol (n = 1,257), or mild ovarian stimulation (n = 216). INTERVENTION(S) The three ovarian-stimulation protocols described and assisted reproductive technology (ART) treatment (IVF or ICSI, and vitrified ET) in ordinary practice. MAIN OUTCOME MEASURE(S) The main measures were: gestational age, birth weight and length, multiple delivery, early neonatal mortality, and birth defects. Associations were assessed using logistic regression by adjusting for confounding factors. RESULT(S) The final sample included 2,060 live-born infants, corresponding to 1,622 frozen-thawed (FET) cycles, which led to: 587 live-born infants from LPS (458 FET cycles); 1,257 live-born infants from the short protocol (984 FET cycles); and 216 live-born infants from mild ovarian stimulation (180 FET cycles). Birth characteristics regarding gestational age, birth weight and length, multiple delivery, and early neonatal death were comparable in all groups. The incidence of live-birth defects among the LPS group (1.02%) and the short GnRH-a protocol group (0.64%) was slightly higher than in the mild ovarian-stimulation group (0.46%). However, none of these differences reached statistical significance. For congenital malformations, the risk significantly increased for the infertility-duration factor and multiple births; the adjusted odds ratios were 1.161 (95% confidence interval [CI]: 1.009-1.335) and 3.899 (95% CI: 1.179-12.896), respectively. No associations were found between congenital birth defects and various ovarian-stimulation regimens, maternal age, body mass index, parity, insemination method, or infant gender. CONCLUSION(S) To date, the data do not indicate an elevated rate of abnormality at birth after LPS, but further study with larger populations is needed to confirm these results. However, infertility itself poses a risk factor for congenital malformation. A higher likelihood of birth defects in multiple births may lead couples to favor elective, single ET; couples undertaking ART should be made aware of the known increased birth defects associated with a twin birth.

Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF: A Double-Blind Randomized Crossover Clinical Trial.

AbstractOvarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies indicated that progestin can prevent premature luteinizing hormone (LH) surge or moderate/severe OHSS in the general subfertile population, both in the follicular-phase and luteal-phase ovarian stimulation but it is unclear if this is true for patients with PCOS.The aim of the article was to analyze cycle characteristics and endocrinological profiles using human menopausal gonadotropin (hMG) in combination with medroxyprogesterone acetate (MPA) for PCOS patients who are undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments and investigate the subsequently pregnancy outcomes of frozen embryo transfer (FET).In the randomized prospective controlled study, 120 PCOS patients undergoing IVF/ICSI were recruited and randomly classified into 2 groups according to the ovarian stimulation protocols: hMG and MPA (group A, n = 60) or short protocol (group B, n = 60).In the study group, hMG (150–225IU) and MPA (10 mg/d) were administered simultaneously beginning on cycle day 3. Ovulation was cotriggered by a gonadotropinreleasing hormone (GnRH) agonist (0.1 mg) and hCG (1000IU) when dominant follicles matured. A short protocol was used as a control.The primary end-point was the ongoing pregnancy rate per transfer and incidence of OHSS.Doses of hMG administrated in group A are significantly higher than those in the controls. LH suppression persisted during ovarian stimulation and no incidence of premature LH surge was seen in both groups. The fertilization rate and the ongoing pregnant rate in the study group were higher than that in the control. The number of oocytes retrieved, mature oocytes, clinical pregnancy rates per transfer, implantation rates, and cumulative pregnancy rates per patient were comparable between the 2 groups. The incidence of OHSS was low between the 2 groups, with no significant difference.The study showed that MPA has the advantages of an oral administration route, easy access, more control over LH levels. A possible reduction in the incidence of moderate or severe OHSS with the MPA protocol should be viewed with caution as the data is small. Large randomized trials with adequate sample size remain necessary.

Luteal-phase ovarian stimulation vs conventional ovarian stimulation in patients with normal ovarian reserve treated for IVF: a large retrospective cohort study.

We have previously reported a new luteal‐phase ovarian stimulation (LPS) strategy for infertility treatment. The purpose of this study was to systematically assess the efficiency and safety of this strategy by comparing it with conventional ovarian stimulation protocols.

Emergency contraceptive use among 5677 women seeking abortion in Shanghai, China

BACKGROUND The increasing use of emergency contraceptive pills (ECPs) does not seem to reduce the number of induced abortions as would be expected, indicating that women use ECPs might also be a strong factor affecting their final efficacy. The study aimed to understand the attitude towards, and use of, ECPs among women seeking an abortion. METHODS A cohort study was conducted via face-to-face questionnaire interview among women seeking abortion in Shanghai, China. Logistic regression analysis and chi(2) test were performed for statistical analysis. RESULTS The response rate was 99.3%. Among all 5677 respondents aged 15-48 years, 48.8% were ECP ever-users. Compared with ever-users, ECP never-users were less likely to have used contraception during the present cycle of conception (P < 0.001). In response to the question on the main reason for non-use of contraception, ECP never-users were less likely to realize the risk of pregnancy and had less contraceptive knowledge (P < 0.001). Among 2773 ECP ever-users, 72.7% did not use ECPs to prevent the current pregnancy, mainly due to lack of awareness of pregnancy risk. Out of 757 women, 437 (57.7%) repeated unprotected sex after taking ECPs during the current pregnant cycle. A pharmacy was the preferred source to access ECPs, for the reason of convenience. CONCLUSIONS Non-use of ECPs was correlated to less knowledge on fertility and a lower rate of contraceptive use among abortion-seeking women. Women of reproductive age should have access to ECPs and receive sufficient information on their use. Health care providers and pharmacists should also be trained in contraceptive counselling, including ECPs.

Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles.

To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1–1.5 ng/ml (including 1), between 1.5–2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1–1.5 ng/mL, between 1.5–2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.

Dual trigger for final oocyte maturation improves the oocyte retrieval rate of suboptimal responders to gonadotropin-releasing hormone agonist

OBJECTIVE To identify the risk factors for suboptimal response to GnRH agonist (GnRH-a) trigger and evaluate the effect of hCG on the outcome of patients with suboptimal response to GnRH-a. DESIGN A retrospective data analysis. SETTING A tertiary-care academic medical center. PATIENT(S) A total of 8,092 women undergoing 8,970 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles. INTERVENTION(S) All women underwent hMG + medroxyprogesterone acetate (MPA)/P treatment cycles during IVF/ICSI, which were triggered using a GnRH-a alone or in combination with hCG (1,000, 2,000, or 5,000 IU). Viable embryos were cryopreserved for later transfer. MAIN OUTCOME MEASURE(S) The rates of oocyte retrieval, mature oocytes, fertilization, and the number of oocytes retrieved, mature oocytes, and embryos frozen. RESULT(S) In total, 2.71% (243/8,970) of patients exhibited a suboptimal response to GnRH-a. The suboptimal responders (LH ≤15 mIU/mL) had a significantly lower oocyte retrieval rate (48.16% vs. 68.26%), fewer mature oocytes (4.10 vs. 8.29), and fewer frozen embryos (2.32 vs. 3.54) than the appropriate responders. Basal LH levels served as the single most valuable marker for differentiating suboptimal responders with the areas under the receiver operating curve of 0.805. Administering dual trigger (GnRH-a and hCG 1,000, 2,000, 5,000 IU) significantly increased oocyte retrieval rates (60.04% vs. 48.16%; 68.13% vs. 48.16%; and 65.76% vs. 48.16%, respectively) in patients with a suboptimal response. CONCLUSION(S) Basal LH level was useful predictor of the suboptimal response to GnRH-a trigger. Administrating dual trigger including 1,000 IU hCG for final oocyte maturation could improve the oocytes retrieval rate of GnRH-a suboptimal responder.

Live birth rates in the first complete IVF cycle among 20 687 women using a freeze-all strategy

STUDY QUESTION What is the chance of having a child following one complete IVF cycle for patients using a freeze-all strategy? SUMMARY ANSWER The chance of having a child after the first complete IVF cycle was 50.74% with the freeze-all strategy. WHAT IS KNOWN ALREADY Several studies have reported on live birth rates (LBRs) based on only the fresh embryo transfer cycle or fresh and frozen-thawed embryo transfer cycles. However, the LBR using a freeze-all strategy in IVF is unknown. STUDY DESIGN SIZE AND DURATION This retrospective cohort study included 20 687 women who started their first IVF cycles using a freeze-all strategy during the period from 1 January 2007, through 31 March 2016, in China. PARTICIPANTS /MATERIALS, SETTING, METHODS Data on 20 687 women undergoing their first complete cycles using a freeze-all strategy from 2007 to 2016 were analyzed to estimate LBRs. The LBR in a complete cycle was defined as the chance of a live birth from an ovarian stimulation cycle including all subsequent frozen embryo transfers from this stimulation. The relationship between LBR and number of oocyte was explored. MAIN RESULTS AND THE ROLE OF CHANCE The LBR for the first complete cycle was 50.74% for patients using a freeze-all strategy. By age group, the LBR declined from 63.81% for women under 31 years old to 4.71% for women over 40 years old after the first complete cycle. The LBRs improved as the number of oocytes retrieved increased up to 25 in the freeze-all strategy. LIMITATION AND REASONS FOR CAUTION This was a retrospective study without a control group. Data on BMI and smoking status were not collected in this database. WIDER IMPLICATIONS OF THE FINDINGS Our results showed that 50.74% of patients could achieve a live birth after the first complete cycle via a freeze-all strategy. In addition, the LBRs were positively correlated with the number of oocytes retrieved via the freeze-all strategy. These findings are critical for patients and clinicians in making an informed decision to embark on IVF treatment. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.) and the Shanghai Ninth Peoples Hospital Foundation of China (JYLJ030 to Y.W.). None of the authors have any conflicts of interest to declare.