Akademik Veri Yönetim Sistemi
International Pelvic Pain Kongresi, İstanbul, Türkiye, 6 - 09 Haziran 2024, ss.10-11
Aim: The empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved in an IVF cycle with an adequate ovarian response to stimulation and careful follicular aspiration. Two variants of EFS have been described. The 'genuine' form (gEFS) occurs in the presence of adequate circulating HCG levels at the time of oocyte aspiration. However, the 'false' form (f-EFS) is associated with circulating HCG below a critical threshold. The false form can somehow be treated, but, the causes of genuine form are not totally understood and the treatment is compelling. We herein present a case of genuine EFS with ZP-1 mutation.
Method: A couple with 3 years of primary infertility admitted to our infertility and reproductive endocrinology unit. The woman was 28 years old, apparently healthy, with normal menstrual cycles, normal physical examination and pelvic sonography. Her baseline investigations were all within normal limits. Her medical and surgical past were unremarkable. The man was a 29-year-old male patient with normal semen analysis; sperm count 37 million sperm per ejaculate, 62% forward motility, 4% normal morphology. With the diagnosis of unexplained infertility, the couple underwent 2 cycles of superovulation and in utero insemination therapy, and as a result of failure to achieve pregnancy, ICSI was recommended.
1st IVF cycle was the antagonist protocol. She received 225 IU units/day recombinant gonadotropin for 10 days. Ovarian stimulation was achieved with gonadotropins (Follitrophin alpha, Gonal-f, Merck) and patient developed 8 follicles. Once the mature follicles reached 18 mm, 0.25 mg synthetic hCG was administrated and oocyte pick-up (OPU) was performed 35 hours later. No oocytes were retrieved from one of the ovaries. With the diagnosis of EFS, a second 0.25 mcg hCG injection was repeated and OPU of the other ovary was performed the next day. Again, no oocytes were retrieved.
In the 2nd IVF cycle; 2 months after the first trial, the patient was given recombinant gonadotropin for 13 days and 2 doses of rec hCG were injected. Ovarian stimulation was achieved with gonadotropins and patient developed 5 follicles.No oocytes were obtained after oocytes pick-up. An additional third cycle yielded no oocytes. After multiple ovarian hyperstimulation protocols with adequate response and meticulous OPU procedures, neither oocytes nor cumulus ± corona complexes were recovered. The patient was referred to the genetic tests with the diagnosis of genuine EFS.
Findings:
To investigate the mutation in the ZP-1 gene in karyotype analysis and whole genome sequence analysis (TED),Sanger sequence and segregation analysis were performed on the peripheral blood of the female patient, her mother and her father. The female patient's karyotype analysis was 46,XX, the male patient's karyotype analysis was 46,XY. In the TED analysis, the exon in the female patient's ZP-1(11q12.2,zona pellucida glycoprotein 1,NM_207341.3,NP_997224.2) gene homozygous c.628>T (p.Q210*,rs776515172) change was detected in her, her mother and her father. It was determined that the mother and father of the female patient carried the same index heterozygously. True empty follicle syndrome has been attributed to genetic basis.
Conclusion: In cases of genuine EFS, there is an intrinsic ovarian pathology causing defective follicular development and a probable genetic cause that needs to be highlighted. Genuine EFS cases can be further evaluated to find out the underlying genetic etyology.