Materials and Methods
Study population
This is a retrospective cohort study. Patients were treated with routine
practice of IVF from July 2016 to December 2018 at Mei-Tsun Reproductive
Medical Center. The data was collected from medical records and the
computerized database. The definition of a poor responder fits into at
least two of the following criteria: (1) A previous episode of poor
ovarian response (≤3 oocytes) under a standard dose of medication; (2)
An abnormal ovarian reserve with AFC (Antral Follicle Counts)
<5–7 follicles or AMH (Anti-Mullerian Hormone)
<0.5–1.1 ng/mL; (3) Women above 40 years of age or those with
other risk factors for poor response such as previous ovarian surgery,
genetic defects, chemotherapy, radiotherapy, and autoimmune disorders.
Patient characteristics including age, body mass index (BMI), basal AFC,
and basal hormone levels were recorded. Clinical parameters including
gonadotropin dosage, E2 levels at human chorionic gonadotropin (hCG)
day, number of oocytes retrieved, fertilization rate, clinical pregnancy
rate, and live birth rates were analyzed.
Supplementation
Each patient received dehydroepiandrosterone (DHEA 30mg, Wild Yam Root
extract, VIVA Pharmaceutical Inc., Canada) 90 mg daily from 3 months
prior to starting IVF cycle until the day of human chorionic
gonadotropin (hCG) trigger. Metformin (Metformin Hydrochloride 500 mg ,
Swiss Pharmaceutical Co.,Ltd , Taiwan ) was given to the patients 1500mg
daily from 3 months prior to starting IVF cycle until a positive
pregnancy test or menstrual bleeding appeared.
IVF process
Controlled ovarian hyperstimulation was performed using the short GnRH
agonist protocol. Buserelin nasal spray (Buserelin acetate 10.5mg,
Sanofi-Aventis Deutschland GmbH , Germany), 300μg three times daily, was
administered from day 2 of treatment cycle until the day human chorionic
gonadotropin (hCG) trigger. Ovarian stimulation was achieved the next
day with 300 IU dose recombinant FSH (rFSH: Gonal-f® ,
Merck-Serono, Geneva, Switzerland, or Puregone® , Organon,
Espanola S.A., Barcelona, Spain) and 150 IU dose hMG
(Pergovaris , 150 rFSH+75 rLH, Merck Serono, Aubonne,
Switzerland, or Merional , 75 FSH+75 LH, IBSA Institut
Biochimique S.A.,Switzerland ). The selection of the type of
gonadotropin was individualized according to each patient’s
characteristics. Serial folliculometry and assessment of serum E2, P4
and LH levels were monitored every 1-2 days, starting from 3-5 days
after stimulation and continued until two or more follicles reached 17
mm in diameter or when per-follicle E2 level reached 200 pg/ml. Dual
trigger, combined recombinant hCG (Ovidrel® 250μg,
Merck-Serono, Geneva, Switzerland) and GnRH agonist (Lupro 2
mg, Nang Kuang Pharmaceutical Co, Ltd., Tainan, Taiwan), were
administered. Oocytes were retrieved 34–36 hours after oocyte trigger
under the guidance of transvaginal ultrasound. Intracytoplasmic sperm
injection (ICSI) was performed in all patients to diminish potential
fertilization failure. The best morphologically graded embryos from the
stimulated cycle was selected for embryo transfer at 3 days after oocyte
retrieval. Luteal support commenced from the second day after oocyte
retrieval with Crinone 8% Progesterone Vaginal Gel
(Progesterone 90mg, Merck Serono, Hertfordshire, UK) andUtrogestan (Micronised Progesterone 100mg, Arich Enterprise
Co., Ltd., Taiwan). A pregnancy test was carried out 15 days after
embryo transfer. Once a positive pregnancy test was observed,
progesterone was continued until 10-12 weeks of gestation. A clinical
pregnancy was confirmed with the presence of a fetal heart beat at 7
weeks of gestation by ultrasonography. A live birth was defined as
delivery after 24 weeks of gestation.
Statistical analysis
All data were analyzed using the commercially available software package
SPSS (SPSS Inc., Chicago, IL, USA) and presented as mean±standard
deviation or number (%). Statistical analysis was carried out using
Mann-Whitney U test for continuous data and χ2 test for categorical
data. Differences were considered to be significant when p value< 0.05.