Qingqing Hong

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.

The pregnancy outcome of progestin‐primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial

To investigate the clinical outcome and endocrinological characteristics of progestin‐primed ovarian stimulation (PPOS) using 4 versus 10 mg of medroxyprogesterone acetate (MPA) per day in infertile women with normal ovary reserve.

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.

Dual trigger of final oocyte maturation in poor ovarian responders undergoing IVF/ICSI cycles

Previous studies show that a dual trigger ovulation regimen significantly improves number and maturity of retrieved oocytes for normal ovarian responders or patients with history of low oocyte yield. The current retrospective cohort study investigated whether dual trigger of final oocyte maturation may benefit IVF outcomes for poor ovarian responders fulfilling the Bologna criteria. Undertaken between May 2014 and August 2016, the study involved 1350 patients undergoing 1389 IVF/intracytoplasmic sperm injection treatment cycles. Patients triggered with 5000 IU human chorionic gonadotrophin (HCG) alone (328 cycles) were compared with those undergoing dual triggering with 5000 IU HCG plus 0.1 mg gonadotrophin-releasing hormone agonist (GnRHa) (386 cycles) and patients triggered with 10,000 IU HCG (363 cycles) were compared with those undergoing dual triggering with 10,000 IU HCG plus 0.1 mg GnRHa (312 cycles). The dual trigger groups showed significantly higher number of oocytes collected and number of mature oocytes compared with their respective HCG trigger group (P < 0.001). Oocyte retrieval rate and percentage of mature oocytes retrieved were also both significantly higher in the dual trigger groups (P < 0.001). Fertilization rate, number of viable embryos, implantation rate, clinical pregnancy rate and miscarriage rate were not significantly different between groups.

Three-Dimensional HyCoSy With Perfluoropropane-Albumin Microspheres as Contrast Agents and Normal Saline Injections Into the Pelvic Cavity for Morphological Assessment of the Fallopian Tube in Infertile Women: Three-Dimensional HyCoSy for Assessment of Fallopian Tube in Infertile Women

To apply the three‐dimensional (3D) hysterosalpingo‐contrast sonography (HyCoSy) with perfluoropropane‐albumin microspheres as contrast agents and normal saline injections into the pelvic cavity for assessment of the tubal patency and adhesions of fimbrial parts.

Monofollicular Stimulation in PCOS Patients

Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility that affects up to 5–10 % of reproductive-age women. Very few studies have focused on monofollicular stimulation in vitro fertilization (IVF) in PCOS patients till now. The first-line medical ovulation induction therapy to improve fertility outcomes is Clomiphene citrate (CC); the recommended starting dose is 50 mg/day. Letrozole has been shown to have good ovulation rate in CC-resistant PCOS women; 5 mg/day showed an optimal result, with high monofolliculogenesis occurrence in PCOS women. When PCOS patients are undergoing IVF treatment, many of these women exhibit exaggerated response, resulting in an increased risk of ovarian hyperstimulation syndrome (OHSS) and multiple gestations. The transfer of frozen-thawed embryos has important implications for the management of women undergoing ovarian hyperstimulation for IVF. Frozen embryo transfer (FET) endometrial preparation by Letrozole combined with human menopausal gonadotropin (hMG) in PCOS is a novel protocol giving us optimal clinical results. The protocol of Letrozole combined with hMG has the potential to be the first-line treatment option for ovulation induction in PCOS women, while its use in ovarian stimulation for IVF deserves further study.