Study Design and Participants
This is a retrospective study including 336 cases received IVF/ ICSI treatment using GnRH-a Prolonged Protocol from April 2019 to April 2020 in the First Affiliated Hospital of Kunming Medical University.
Inclusion criteria
- The eligible women received their cycles of IVF or ICSI because of tubal factors, male factors, or a combination of both.
- IVF/ICSI-fresh embryo transfer (ET) and an age ≤ 40 years.
- The first cycle of the same patient.
Exclusion criteria
- Patients with a diagnosis of recurrent spontaneous abortion (RSA)
- Couples (either the male or female) with chromosomal abnormalities and a history of cancer were excluded.
- Preimplantation genetic testing (PGT)
- Missing clinical data
- Female age > 40 years
- Sperm donor cycle
Diagnosis of PCOS
Polycystic ovary syndrome diagnosed by modified Rotterdam criteria (Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004,)[11]
Classification of OHSS symptoms
Ttraditionally classified into mild, moderate, severe and critical, based on OHSS prevention and treatment guideline of American Society for Reproductive Medicine[12].
Mild-OHSS: abdominal distension/discomfort, mild nausea/vomiting, mild dyspnea, diarrhea, enlarged ovaries, and no important alterations [12]:
Moderate-OHSS: mild features, ultrasonographic evidence of ascites, hemoconcentration (Hct > 41%), and elevated WBC (> 15,000 mL)[12],
Severe-OHSS: mild and moderate features, clinical evidence of ascites, hydrothorax, severe dyspnea, oliguria/anuria, intractable nausea/vomiting, severe hemoconcentration (Hct > 55%), WBC > 25,000 mL, CrCl < 50 mL/min, Cr > 1.6 mg/dL, Na + < 135 mEq/L, K + > 5 mEq/L, and elevated liver enzymes, critical: low blood/central venous pressure, pleural effusion, rapid weight gain (> 1 kg in 24 h), syncope, severe abdominal pain, venous thrombosis, anuria/acute renal failure, arrhythmia, thromboembolism, pericardial effusion, massive hydrothorax, arterial thrombosis, adult respiratory distress syndrome, sepsis, and worsening of findings[12].
Measurements and laboratory analyses
Gonadal hormone concentrations and AMH measurements were performed on the serum of each subjects. Level of AMH will be examined using a Gen 2 ELISA kit (Beckman Coulter, Inc. Brea, CA, USA). Serum was stored at −70℃. A combined gas chromatographic negative ionization tandem mass spectrometry and liquid chromatographic electrospray tandem mass spectrometry bioanalytical method was used to measure Gonadal hormone (Taylor Technology, Princeton NJ).
Early-Follicular Phase Gonadotropin-Releasing Hormone Agonist (GnRH-a) Prolonged Protocol
One depot of 3.75 mg GnRH-a was injected on day 2 of the menstrual cycle, 35 days later, pituitary downregulation was confrmed (no follicular diameter >8 mm, E2<50 pg/ml), Gonadotropin (rFSH-Gonal-f Merck Serono, Germany) was used at an initiative dose ranging from 150–225 U. The dose of Gn was adjusted according to the size, counts of follicles and hormone levels. When 2 dominant follicles reached 18 mm in diameter, or three follicles = >17 mm, human chorionic gonadotrophin (HCG, 5000–10,000 IU, Lizhu Pharmaceutical Trading Co., German) was administered for trigger ovulation[13].
If number of oocytes retrieved ≥15, the serum E2 ≥ 5000 pg/ml on hCG trigger day or the serum E2 ≥ 1500 pg/ml on the second day after oocyte retrieval, or OHSS manifestations such as nausea, vomiting, abdominal pain and distension appeared, patients would receive a “freeze-all” approach instead of fresh embryo transfer to prevent late OHSS[12].
There were 61 cases of OHSS and 275 cases of non-OHSS. The database was collected after the approval of the medical ethics committee. All data were collected from the electronic medical record system and adjusted by at least two authors.
All of the included patients read and signed the informed consent form. This retrospective study was approved by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University. All the treatments in the present study were performed strictly in accordance with the Declaration of Helsinki for Medical Research.
Statistical analysis
All analyses were performed using SPSS 22.0 statistical software package (SPSS Inc, Chicago, IL). According to the distribution of data types to choose the appropriate statistical methods to analyze the differences between groups, two independent groups were assessed using Student's t‐test or the Wilcoxon rank‐sum test. We constructed a multivariable logistic regression model by including each of the conditions as independent variables. The dependent outcome variable was OHSS or not. Receiver operating characteristic (ROC) analysis was carried out and area under the curve (AUC) was compared to evaluate the predicting ability of clinical indicators scores. Based on the cut-off values, sensitivity and specificity were also calculated. A Z test was used for comparing the AUCs between different curves. The Bonferroni method was used adjust for multiple comparisons.