Clinical trial: Biosimilarity Study of IM Injection of Human Chorionic Gonadotrophin After Parenteral Administration of Treatment A TEST Product Epifasi 5000 I.U. Ampoules (EIPICO PHARMA, EGYPT) and Treatment B REFERENCE Product Pregnyl 5000 I.U. Ampoules (Baxter Pharmaceutical Solutions for Organon, USA). (NCT04605107)

Eligibility criteria:
Inclusion Criteria:

          1. Premenopausal woman between 18 - 40 years of age.

          2. Body mass index (BMI) of 32 or less.

          3. A menstrual cycle lasting between 21 and 35 days.

          4. Serum hormone levels of FSH 12 IU/L or less, PRL 1040 mIU/L or less, and TSH within
             the normal range of 0.3- 4.9 mIU/L

          5. Patient having both ovaries and a normal uterine cavity confirmed by hysteroscopy, or
             hysterosalpingography.

          6. All patients had to be infertile due to at least one of the following causes and must
             have justified ART (Assisted Reproductive Technology) treatment: tubal factor, mild
             endometriosis (American Fertility Society classification stage I orII), unexplained
             infertility, or male factor

          7. Patients achieving good ovarian response and considered to receive hCG for final
             follicular maturation prior to OPU.

          8. Written and signed informed consent by the patient.

          9. Subject does not have allergy to the drugs under investigation.

         10. Medical demographics without evidence of clinically significant deviation from rather
             normal medical condition.

        Exclusion Criteria:

          1. Patients with low ovarian reserve, as proved by hormonal assays and basal antral
             follicular count.

          2. More than three previous assisted reproductive technology cycle or treatment with
             clomiphene citrate or gonadotropins for at least 1 month before screening,

          3. Patients with pelvic abnormality that would interfere with ovarian accessibility for
             OPU, e.g. ovarian endometriotic cysts or high and retro-uterine ovary.

          4. Patients not achieving a satisfactory ovarian response on ovulation induction, whether
             poor response (3 or less mature ovarian follicles) or over-response with high
             likelihood of developing ovarian hyperstimulation syndrome (OHSS) on triggering with
             HCG.

          5. History of hypersensitivity to the study medications or to drugs with similar chemical
             structure.

          6. Patients unlikely to comply with the protocol, e.g. uncooperative attitude, inability
             to return for follow-up visits, and likelihood of not completing the study.

          7. Mental condition rendering the patients unable to understand the nature, scope and
             possible consequences of the study.

          8. Results of laboratory tests which are clinically significant.

          9. Acute infection within one week preceding first study drug administration.

         10. History of drug or alcohol abuse.

         11. Subject does not agree not to take any prescription or non-prescription drugs within
             two weeks before first study drug administration and until the end of the study.

         12. Subject is on a special diet (for example subject is vegetarian).

         13. Subject does not agree not to consume any beverages or foods containing
             methyl-xanthenes e.g. caffeine (coffee, tea, cola, chocolate etc.) 48 hours prior to
             the study administration of either study period until donating the last sample in each
             respective period.

         14. Subject does not agree not to consume any beverages or foods containing grapefruit 7
             days prior to first study drug administration until the end of the study.

         15. Subject has a history of severe diseases which have direct impact on the study.

         16. Participation in a biosimilarity study or in a clinical study within the last 6 weeks
             before first study drug administration.

         17. Subject intends to be hospitalized within 3 months after first study drug
             administration.
Female
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 40 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction