Follicle Aspirating is an Effective Remedy When Multi-follicles Developed in Donor-sperm Timing-Artificial Insemination

Special Article: Multiple Ovulations

Austin J In Vitro Fertili. 2023; 7(1): 1042.

Follicle Aspirating is an Effective Remedy When Multi-follicles Developed in Donor-sperm Timing-Artificial Insemination

Xiao Chen1,2,3; Rong Hua Jiang1,2,3; Xue Jun Zhang1,2,3; Wan Shan Zhu1,2,3; Yu Ting Zhang1,2,3; Yu Liu1,2,3; Ze Rong Zhou1,2,3; Ge Song1,2,3*

¹Reproductive center of Guangdong provincial Fertility Hospital, Guangzhou, China

²Reproductive center of Guangdong provincial Reproductive Science Institute, Guangzhou, China

³Key Laboratory of Male Reproduction and Genetics Health Commission, Guangzhou, China

*Corresponding author: Ge Song Reproductive center of Guangdong provincial Fertility Hospital, N0.17, Meidong Road, Guangzhou, China. Tel: 0086-020-87651527 Email: songpp@126.com

Received: February 24, 2023 Accepted: April 05, 2023 Published: April 12, 2023

Abstract

Purpose: To avoid multi-pregnancy, the cycle usually has to be cancelled when Multi-Follicles Developed (MFD) in artificial insemination. For the strong willing to continue the cycle for most patients, we explored the effectiveness of excess follicles aspirating as another remedy when multiple follicle developed.

Methods: We conducted a retrospective study in patients taking Artificial Insemination with Donor sperm (AID) and ovarian stimulation protocol from 2011 to 2022. Patients were divided in 4 groups according to the differences of receiving aspirating and follicle number. Clinical pregnancy rate, multi-pregnancy rate (twin pregnancy and high order pregnancy, separately) were mainly compared in our study.

Results: When multi-follicles developed, patients taking excess follicle aspirating achieved a comparable clinical pregnancy rate with those without aspirating (30.7% vs 26.1%). These two groups had a similar multi-pregnancy rate, 21.7% and 17.4% respectively, while high order pregnancy was rather lower in excess follicles aspirating group. MFD patients carried a significant higher clinical pregnancy rate, multi-pregnancy rate than patients with two dominate follicles patients under the age of 35. In ovarian stimulation protocol, patients with two dominate follicles carried nearly the same clinical pregnancy rate with one dominate follicle patients (21.4 vs 21.5%). Gemellary pregnancy rate was significant lower in one than two dominate follicles group (7.5% vs 0.4%) when patient’s age was under 35. In the age of 35 or older, the clinical pregnancy rate and multi-pregnancy rate were similar in patients with multi-follicles and two dominate follicles.

Conclusion: In AID, in the age of lower than 35, when multi-follicles developed, excess follicle aspirating with two dominate follicles reserved effectively deceased high order pregnancy and ensured the clinical pregnancy rate at the same time. From the perspective of singleton, it was feasible to keep one dominate follicle reserved.

Keywords: AID; Multi-follicle development; Multi-pregnancy rate; Follicle aspirating

Introduction

For the superiority of low cost and less invasive, Artificial Insemination (AI) is an easy way widely used in infertile couples [1,2]. It is the first choice for infertile couples with male factors such as sexual dysfunction or azoospermatism [3,4]. To ensure pregnancy, the basic essentials are 1. sufficent quantity and quality sperms [5] 2. At least one maturing follicle development and ovulation [6] 3. Proper time and conditions for fertilization [7]. As we known, the quantity and quality of female eggs decrease with age. It was reported that there was only one out of three eggs with high quality [8]. It was commonly accepted for both physicians and patients to achieved more than one follicle by ovulation induction for the aim of getting pregnancy soon. Ovulation induction used to apply to patients with ovulation dysfunction, researchers suggested that it increased clinical pregnancy rate in unexplained infertility patients with normal ovulation [9,10]. However, despite of the influence in clinical pregnancy rate, multi-follicles may lead to the increase of multi-pregnancy.

Multi-pregnancy caused by MFD was the major complication in ovulation induction. It was reported the rate of multiple gestation was 20 to 100 times higher in ovarian stimulation cycles than in nature cycles [11]. As reported, multi-pregnancy, especially high order multiple pregnancy, lead to adverse obstetric outcomes [12,13]. Though, fetal reduction was a measure to improve the outcomes of multi-pregnancy, it didn’t total reverse the undesirable outcomes [14].

Thus, the prevention of multi-pregnancy, especially high order pregnancy becomes more important. Usually, the cycle had to be cancelled when MFD occurred in AI. It was hardships for patients to cancel the cycle, especially for the aged or patients with ovulation dysfunction. For this reason, follicle aspirating as a remedy for MFD in artificial insemination has become increasingly valued. Follicle aspirating was first reported by Christian in 1998 [15]. A few years later, the ASRM suggested it was considerable to aspirate excessive follicles after administration of HCG in 2006 [16]. Regretfully, few researchers reported the details of this measure. It still remained unclear about the effectiveness and the suitable reserved follicle number in excessive follicles aspirating. Thus, we conducted a retrospective study to reveal the effectiveness of extra follicle aspirating and explore the suitable reserved follicle number so as to afford another choice for patients. The clinical pregnancy rate and multi-pregnancy rate were the primary outcomes. We also made a comparison about one and two follicles in donor-sperm artificial insemination as a guidance for the number of follicle reserved in follicle aspirating.

Materials and Methods

We analyzed patients whose oviducts were both unobstructed, taking ovarian stimulation protocol and undergoing Donor-sperm artificial insemination from 2011 to 2022 in reproductive center, Guangdong Provincial Fertility Hospital.

Ovarian Stimulation

The ovarian stimulation protocol included oral drugs (Clomiphene, Letrozole) or Gonadotrophin(Gn) alone and the two combined. Ovarian stimulation was started from day 2 to 4 of menstrual cycle. Follicle development was monitored by transvaginal ultrasonography and Gn dose adjusted every 1 to 3 days by physician’s experience if necessary. The urine Luteinizing Hormone (LH) test paper was tested when the leading follicle reached average diameter of 16mm, there after, serum LH and progesterone were measured when necessary.

Human Chorionic Gonadotropin (HCG) Trigger

The administration of HCG was immediately when the test paper was positive or the leading follicle reached average diameter of 20mm. The dosages of HCG were around 6000-10000iu accordingly.

Follicle Aspirating

From 2020, once there were 3 dominating follicles (average diameter ≥14mm) development; follicle aspirating was conducted after the administration of HCG so that only 2 dominate follicles were reserved. Physicians would try their best to ensure one dominate follicle for each ovary if possible. The concrete operation was similar as oocyte retrieval. The excess follicles (average diameter ≥12mm) were aspirated and abandoned in the operation under the guidance of ultrasound.

Artificial Insemination

The timing artificial insemination was carried out according to the time of HCG administration and serum LH level. To our experience, insemination performed nearly before and after ovulation achieved better results. The sperms were provided by human sperm bank in Guangdong Province.

Luteal Support

Luteal support was started from the first day after ovulation. Patients took up to 400mg progesterone daily for 14 days. Once the pregnancy was confirmed, luteal support went on.

Pregnancy Confirmation

A blood test was drawn to confirm pregnancy for patients. We viewed a uterine pregnancy with babies’ heart as clinical pregnancy.

Basis for group

According to the difference of dominate follicle’s number and whether follicle aspirating was taken, patients were divided into 4 Groups. In group A, there were more than 3 dominate follicles developed in which follicle aspirating were taken while did not in group B. Group C and D included patients with no more than 2 dominate follicles taking ovarian stimulation protocol, one dominate follicle for Group C and 2 for Group D.

Statistical Analysis

Statistical analyses were performed using SPSS software (version 21.0 for Windows®;). Student’s t-test was used for continuous variables and chi-square tests for categorical variables. Continuous variables are presented as mean±SD, categorical variables are presented as rate (%). Two tailed tests were employed, and P<0.05 was considered to indicate statistical significance.

Results

We searched 36267 cycles in the database in our center from 2011 to 2022, a total of 11240 cycles were analyzed in our study.

There were no significant difference in age, basic-FSH level, basic-LH level, endometrial thickness with Group A and Group B. Sperm parameters was significantly better in Group B than in Group A, while, unexpected, the clinical pregnancy rate was comparable in this two groups (30.7% vs 26.1%, p>0.05). With regard to multi-pregnancy, though multi-pregnancy rate were similar (21.7% vs 17.4%, p>0.05), there was no triplet or greater pregnancy in Group A while 19 cases (4.4%) of triplet or greater pregnancy in Group B. All the multi-pregnancy cases in Group A were twins (Table 1).