Please select the eligibility criteria that correspond to the clinical trial below.
Title: Metformin Addition to Gonadotropins Ovarian Stimulation in High Responder Patients With PCOS Undergoing In-vitro Fertilization
Brief Summary: The use of metformin pre-treatment and co-administration was recently proposed in infertile women affected by polycystic ovary syndrome (PCOS) treated with gonadotropins.

Data from meta-analyses showed that metformin administration significantly reduced the stimulation length and the total dose of gonadotropins used in PCOS women undergoing gonadotropins stimulation for non in-vitro fertilization (IVF) cycles. On the other hand, in IVF cycles metformin was demonstrated to significantly reduce the ovarian hyperstimulation syndrome (OHSS) rate in infertile patients with PCOS treated with gonadotropins.

The metformin regulating effect on the ovarian response was also observed in a randomized controlled trial (RCT) on young non-obese insulin-resistant women with PCOS receiving gonadotropins for mono-ovulation induction. In particular, metformin increased the mono-ovulatory cycles, the duration of stimulation and the amount of gonadotropins used, while it reduced the number of dominant follicles and the estradiol (E2) levels.

The aim of the present study was to evaluate the effect of metformin administration in high responder PCOS patients undergoing gonadotropins ovarian stimulation for IVF cycles.


Options:
A: Inclusion Criteria:

* PCOS diagnostic criteria

  * 2003 American Society for Reproductive Medicine(ARSM)/European Society of Human Reproduction and Embryology(ESHRE) consensus meeting guideline
  * include two out of three

    1. Oligo - or anovulation
    2. Clinical or/and biochemical hyperandrogenism
    3. Polycystic ovaries on ultrasound, exclusion of other etiologies( ≥ 12 follicles(2-9 mm diameter) in each ovary or ovarian volume(0.5 x length x width x thickness) ≥ 10cm3)
* Anatomical normal uterus
* Normal level of thyroid hormone

Exclusion Criteria:

* Severe endometriosis(stageIII, IV)
* Endometrial thickness less than 7mm in late follicular phase
* Severe male infertility factor, non-obstructive azoospermia
* History of ectopic pregnancy or abortion over the last 3 months
* Unexplained abnormal uterine bleeding
* Congenital adrenal hyperplasia
* Androgen secreting tumor
* Cushing syndrome
* Concurrent administration of metformin, ovulation induction drugs, oral contraceptives within previous 3 months
* Chronic disease(liver, kidney, severe heart failure, DM)
* Any pathology of genital tract
* History of alcohol abuse
* Refuse of study participate consent
B: Inclusion Criteria:

* History of one previous cancelled cycle for high-risk of OHSS, or history of moderate/severe OHSS during their previous IVF cycle
* Infertility
* Polycystic ovary syndrome (PCOS)
* insulin resistance
* hyperandrogenism

Exclusion Criteria:

* BMI\>30 kg/m2
* age \>35 years
* FSH\>9UI/L
C: Inclusion Criteria:

* Infertile women applied to assisted reproduction clinic
* Follicle stimulating hormone \< 12
* Body mass index \< 25
* Patients whom antagonist protocol will be used
* Patients whom at least 2 good-quality embryos obtained
* Patients who are volunteer

Exclusion Criteria:

* Severe male factor (Sperm concentration \<5 M/ml, progressive sperm motility \<%10)
* Uterine anomaly
* Hydrosalphynx
* Difficult embryo transfer
* Patients who previously had a diagnosis of endometriosis and / or adenomyosis
* Endocrine problems (hypothyroidism, hyperthyroidism, hyperprolactinemia, premature ovarian insufficiency)
* Having more than 3 in vitro fertilization failure
* Refusing to participate
D: Inclusion Criteria:

1. 3 or more than 3 embryo implantation failure histories previously (or the number of high-quality embryos transplanted is \>4);
2. Age \<40 years；
3. Ultrasound or HSG showed normal uterine cavity, endometrium on transplantation day is ≥ 8mm;
4. There's at least one good quality embryo on transplantation day.

Exclusion Criteria:

1. Patients using donor sperm or donor eggs;
2. Patients have obvious uterine cavity abnormalities;
3. There was a clear hydrosalpinx;
4. Natural cycles or IVM patients;
5. Patients who cancel the due to the transfer due to various reasons, such as the failure of fertilization, or ovarian transitional stimulus syndrome (OHSS);
6. Abnormal karyotype;
7. Blastocyst transplantation patients.

Answer: B