• 제목/요약/키워드: Severe male factor infertility

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한국인 남성 불임환자에서 Y염색체내 미세결실의 분자유전학적 분석 (Molecular Genetic Analysis of Microdeletions in Y Chromosome from Korean Male Infertility Patients)

  • 윤현수;이정현;서주태;김해정;이동률;전종식;조정현;김문규;이무상;노성일
    • Clinical and Experimental Reproductive Medicine
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    • 제23권3호
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    • pp.367-377
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    • 1996
  • Genes on the long arm of Y chromosome, particularly interval 6, are believed to playa critical role in human spermatogenesis. The objective of this study was to validate a sequenced-tagged site(STS)-mapping strategy for the detection of Yq microdeletion and to use this method to determine the proportion of men with Yq microdeletions in idiopathic, obstructive, nonobstructive azoospermia, severe OATS and in normal males. We analyzed three STS markers mapped to interval 6 within long arm of the Y chromosome from 106 nonobstructive, 30 obstructive azoospermia, 15 severe OATS patients, and normal 42 males in Korean men. By PCR, we tested leukocyte DNA, for the presences of STS markers(DAZ, sY129 and sY134) and SRY gene as internal control. And PCR results were confirmed by Southern hybridization, and were investigated by SSCP analysis for DAZ gene mutation. None of 42 normal males and 30 obstructive azoospermia had microdeletions, Of the 15 severe OATS typed with DAZ, sY129 and sY134, 3(20.0%) patients failed to amplify 1 or more STS markers, and of the 106 nonobstructive azoospermia typed with DAZ, sY129 and sY134, 12(11.3%) patients failed to amplify 1 or more STS markers. From these results, high prevalence(12.4%) of Yq deletion(DAZ, sY129, sY134) in men with nonobstructive idopathic azoospermia and severe OATS were observed in Korean infertility patients. To avoid the infertile offspring by assisted reproductive technique using ICSI or ROSI, genetic diagnosis will be needed in IVF-ET program.

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ICSI시대에서의 남성불임 (Male Infertility in the Era of ICSI)

  • 서주태
    • 대한생식의학회:학술대회논문집
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    • 대한불임학회 2003년도 제45차 추계학술대회
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    • pp.21-30
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    • 2003
  • As a result of the technological advance provided by intracytoplasmic sperm injection (ICSI) in 1992, the evaluation and treatment of the infertile male has changed significantly. Many men who were previously thought to be irreversibly infertile have the potential to initiate their own biologic pregnancy. However, not all men having impaired semen parameter are ideal candidates for ICSI for numerous reasons including a lack of addressing the underlying problem causing the male infertility, unknown genetic consequences, and cost-effectiveness issues. In this era of ICSI, the fundamental approach to the male with suspected subfertility is unchanged and is based on a history, physical examination, and focused laboratory testing. The urologist should approach the patient with an intent to identify remediable causes of subfertility given the specific clinical situation. For instance, should a gentleman have his varicocele repaired or vasectomy reversed, or should he proceed directly with ICSI? If no factors can be improved in a timely manner, then ICSI should be considered using the available sperm. Examples of recent advances include the diagnosis and treatment of ejaculatory duct obstruction, indications and techniques for performing testis biopsy, and technique for sperm harvesting. In addition, potential genetic causes of male subfertility should be diagnosed and discussed with the patient. Cystic fibrosis gene mutation, karyotype abnormallities, and Y-chromosome microdeletions all have recently been identified as causative for male infertility in otherwise phenotypically normal men. With recently evolved diagnostic and therapeutic techniques now available for the infertile couple, even the most severe male factor problems in patients previously considered irreversibly infertile are now potentially treatable. The physician should be aware of the availability and limitations of these new and exciting reproductive technologies because they will allow him to provide timely and more effective therapy for the infertile couple. An understanding of these advances by all physicians is important as we progress into the $21^{st}$ century

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Misuse of testosterone replacement therapy in men in infertile couples and its influence on infertility treatment

  • Song, Seung-Hun;Sung, Suye;Her, Young Sun;Oh, Mihee;Shin, Dong Hyuk;Lee, Jinil;Baek, Jeongwon;Lee, Woo Sik;Kim, Dong Suk
    • Clinical and Experimental Reproductive Medicine
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    • 제46권4호
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    • pp.173-177
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    • 2019
  • Objective: We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples. Methods: This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (< 5 × 106/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded. Results: The mean age of patients was 37 years and the mean duration of infertility was 16.3 ± 11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months. Conclusion: TRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient's desire for fertility must be considered before initiation of TRT in a hypogonadal man.

Artificial oocyte activation in intracytoplasmic sperm injection cycles using testicular sperm in human in vitro fertilization

  • Kang, Hee Jung;Lee, Sun-Hee;Park, Yong-Seog;Lim, Chun Kyu;Ko, Duck Sung;Yang, Kwang Moon;Park, Dong-Wook
    • Clinical and Experimental Reproductive Medicine
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    • 제42권2호
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    • pp.45-50
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    • 2015
  • Objective: Artificial oocyte activation (AOA) is an effective method to avoid total fertilization failure in human in vitro fertilization-embryo transfer (IVF-ET) cycles. AOA performed using a calcium ionophore can induce calcium oscillation in oocytes and initiate the fertilization process. We evaluated the usefulness of AOA with a calcium ionophore in cases of total fertilization failure in previous cycles and in cases of severe male factor infertility patients with non-motile spermatozoa after pentoxifylline (PF) treatment. Methods: The present study describes 29 intracytoplasmic sperm injection (ICSI)-AOA cycles involving male factor infertility at Cheil General Hospital from January 2006 to June 2013. Patients were divided into two groups (control, n=480; AOA, n=29) depending on whether or not AOA using a calcium ionophore (A23187) was performed after testicular sperm extraction-ICSI (TESE-ICSI). The AOA group was further split into subgroups according to sperm motility after PF treatment: i.e., motile sperm-injected (n=12) and non-motile sperm-injected (n=17) groups (total n=29 cycles). Results: The good embryo rate (52.3% vs. 66.9%), pregnancy rate (20.7% vs. 52.1%), and delivery rate (10.3% vs. 40.8%) were lower in the PF/AOA group than in the control group. When evaluating the effects of restoration of sperm motility after PF treatment on clinical outcomes there was no difference in fertilization rate (66.6% vs. 64.7% in non-motile and motile sperm, respectively), pregnancy rate (17.6% vs. 33.3%), or delivery rate (5.9% vs. 16.7%) between the two groups. Conclusion: We suggest that oocyte activation is a useful method to ensure fertilization in TESE-ICSI cycles regardless of restoration of sperm motility after PF treatment. AOA may be useful in selected patients who have a low fertilization rate or total fertilization failure.

Clinical outcomes of preimplantation genetic testing for aneuploidy in high-risk patients: A retrospective cohort study

  • Jun Woo Kim;So Young Lee;Chang Young Hur;Jin Ho Lim;Choon Keun Park
    • Clinical and Experimental Reproductive Medicine
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    • 제51권1호
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    • pp.75-84
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    • 2024
  • Objective: The purpose of this study was to evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on clinical outcomes among high-risk patients. Methods: This retrospective study involved 1,368 patients and the same number of cycles, including 520 cycles with PGT-A and 848 cycles without PGT-A. The study participants comprised women of advanced maternal age (AMA) and those affected by recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or severe male factor infertility (SMF). Results: PGT-A was associated with significant improvements in the implantation rate (IR) and the ongoing pregnancy rate/live birth rate (OPR/LBR) per embryo transfer cycle in the AMA (39.3% vs. 16.2% [p<0.001] and 42.0% vs. 21.8% [p<0.001], respectively), RIF (41.7% vs. 22.0% [p<0.001] and 47.0% vs. 28.6% [p<0.001], respectively), and RPL (45.6% vs. 19.5% [p<0.001] and 49.1% vs. 24.2% [p<0.001], respectively) groups, as well as the IR in the SMF group (43.3% vs. 26.5%, p=0.011). Additionally, PGT-A was associated with lower overall incidence rates of early pregnancy loss in the AMA (16.7% vs. 34.3%, p=0.001) and RPL (16.7% vs. 50.0%, p<0.001) groups. However, the OPR/LBR per total cycle across all PGT-A groups did not significantly exceed that for the non-PGT-A groups. Conclusion: PGT-A demonstrated beneficial effects in high-risk patients. However, our findings indicate that these benefits are more pronounced in carefully selected candidates than in the entire high-risk patient population.

투명대하 미세수정(SUZI)시 정자의 상태 및 처리방법에 따른 수정률과 임신률 (Influence of Sperm Parameters and Capacitation Methods on the Outcome of Subzonal Insemination(SUZI))

  • 최규완;김수경;양현원;차영범;이승재;박종민;김문규
    • Clinical and Experimental Reproductive Medicine
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    • 제21권1호
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    • pp.21-29
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    • 1994
  • Subzonal insemination(SUZI) has been proposed for patients with severe male factor and previous fertilization failure. However, very low fertilization rates still persisted. The aims of this study were firstly, to examine the relationships between the fertilization rate and sperm parmeters, sperm incubation media and time, secondly, to evaluate the outcome of 119 cycles of SUZI applied the modified sperm preparation method. The fertilization rates were influenced more sensitively by sperm preincubation media and time than by sperm parameters. According to preincubation media and time, the fertilization rates were 43.3% in 50% follicular fluid (HFF), 36.6% in 10% fetal cord serum(FCS), and with the time, increased in FCS, but decreased in HFF. In regrd with sperm parameters, the fertilization rates were 42.9% in normal and 37.6% in subnormal group. The best results were obtained from SUZI by the spermatozoa incubated in 50% HFF for 6-8 hours. So we tried 119 cycles of SUZI(normal; 39 cycles, subnormal; 80 cycles) using the preparation method of 6-8 hour incubation in 50% HFF. There were no signigicant differences in the fertilization rates between normal(125/269, 46.4%) and subnormal sperm(264/635, 41.6%). Contrary to the fertilization rates, pregnancy outcomes were different between both groups. Better results obtained from the subnormal group than the normal in the number of transferred embryos, that of good embryos, and developmental rate of the fertilized eggs. The pregnancy rates per transfer were totally 13.3%(13/98),20.0%(13/65) in subnormal group. In the normal group, 2 patients showed ${\beta}$-hCG positive, but resulted in chemical pregnancy. Of 13 clinical pregnancies, two aborted, 6 on-going, and 5 delivered. In conclusion, SUZI is an effective technique to overcome fertilization failure for male factor and unexplained. The fertilization rate is influenced by sperm parameters, sperm incubation media and time. Also the quality of oocytes might be important for pregnancy as same as that of sperm.

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자궁강내 인공수정에 의한 임신율 (Pregnancy Rate by Intrauterine Insemination (IUI) with Controlled Ovarian Hyperstimulation (COH))

  • 홍정의;이지삼
    • Clinical and Experimental Reproductive Medicine
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    • 제25권2호
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    • pp.217-231
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    • 1998
  • The effectiveness of intrauterine insemination (IUI) combined with controlled ovanan hyperstimulation (COH) in the treatment of infertility with various etiologies was compared in a total of 152 cycles. Patients received a maximum of three IUI cycles for the treatment. Severe male ($<2\times10^6$ motile sperm) or age factor (> 39 y) patients were excluded in this study. Pregnancy was classified as clinical if a gestational sac was seen on ultrasound. The overall clinical pregnancy rate was 7.9% per cycle (12/152) and 9.7% per patient (12/124). The pregnancy rates were 0% in unstimulated natural (0/18), 7.5% in CC (3/40), 8.2% in CC+hMG (4/49), 5.9% in GnRH-a ultrashort (1/17), 5.9% in GnRH-a long (1/17) and 27.3% in dual suppression cycles (3/11), respectively. The pregnancy rate was higher in dual suppression cycle than other stimulated cycles, but this was not significant. The multiple pregnancy rates were 25.0% (2 twins and 1 triplet). No patient developed ovarian hyperstimulation. Abortion rates were 66.7% in CC (2/3) and 100% in ultrashort cycles (1/1). The livebirth rate was 5.9% per cycle (9/152) and 7.3% per patient (9/124). There were no differences in age, duration of infertility, follicle size, total ampules of gonadotropins and days of stimulation between pregnant and non-pregnant groups. However, significant(P<0.05) differences were observed in the level of estradiol $(E_2)$ on the day of hCG injection ($3,266.6{\pm}214.2$ vs $2,202.7{\pm}139.4$ pg/ml) and total motile sperm count ($212.1{\pm}63.4$ vs $105.1{\pm}9.9\times10^6$) between pregnant group and non-pregnant group. These results suggest that IUI combined with successful ovarian stimulation tends to improve the chance of pregnancy as compared to IUI without COH and a total motile sperm count may be considered predictive of the success for pregnancy.

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Clomiphene Citrate와 성선자극호르몬을 병합한 배란유도주기에서 성교와 인공수정에 의한 임신율의 비교 (Pregnancy Rate by Intrauterine Insemination (IUI) or Timed-Intercourse In Stimulated Cycles with Clomiphene Citrate and Gonadotropins)

  • 홍정의;이지삼
    • Clinical and Experimental Reproductive Medicine
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    • 제26권1호
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    • pp.31-41
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    • 1999
  • To evaluate the effectiveness of intrauterine insemination (IUI) in the treatment of infertility, timed-intercourse and intrauterine insemination by husband in stimulated cycles with clomiphene citrate and gonadotropins were compared in a total of 105 cycles. Patients received 100mg of clomiphene citrate daily for 5 days starting on day 3 of the menstrual cycle followed by hMG or FSH. Doses of exogenous gonadotropins were adjusted by the follicular development and concentrations of serum estradiol $(E_2)$. More than 3 follicles reaching >16 mm were present in the ovary, 5,000 IU of hCG was administered intramusculary. Patients received a maximum of three intercourse or IUI cycles for the treatment. Severe male (<$10{\times}10^6$ motile sperm) or age factor (>39 y) patients were excluded in this study. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. The overall clinical pregnancy rates were 17.1% per cycle (18/105) and 21.2% per patient (18/85). The pregnancy rates (per cycle) were 17.5% (11/63) in intercourse and 16.7% (7/42) in IUI groups, respectively. IUI had no significant improvement in pregnancy rate compared with timed-intercourse. The multiple pregnancy rates were 11.1% (1 twin and 1 triplet). No patient developed ovarian hyperstimulation. Abortion rate was 28.6% (2/7) in IUI group only. The delivery and ongoing pregnancy rates were 15.2% per cycle (16/105) and 18.8% per patient (16/85). There were no differences in age, duration of infertility, follicle size and level of estradiol $(E_2)$ on the day of hCG injection in pregnant and non-pregnant groups. However, total doses of gonadotropins were higher in pregnant group than in non-pregnant group (p<0.01). Pregnancy rate was not affected by ovulatory status at the time of insemination. These results indicate that well timed-intercourse in stimulated cycles is as effective as IUI for infertile couples.

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Phosphate가 제거된 단순배양액 중 아미노산의 첨가가 체외수정시술 후 임신율에 미치는 영향 (Effects of Amino Acids in Simple Phosphate-Free Media on Pregnancy Rate in Human In Vitro Fertilization and Embryo Transfer(IVF-ET))

  • 이지삼;홍정의;유승환;정구성;홍기언;전은숙;허영문;이종인
    • Clinical and Experimental Reproductive Medicine
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    • 제26권2호
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    • pp.239-249
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    • 1999
  • The role of amino acids in culture media for IVF-ET was examined in a total of 76 cycles. Patients received clomiphene citrate (CC) followed by hMG or GnRH-a combined with gonadotropins (FSH/hMG) for controlled ovarian hyperstimulation. Severe male (<$4{\times}10^6$ motile sperm) or age factor (>39 y) patients were excluded in this study. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. No significant differences were found in age, duration of infertility, follicle size, the level of $E_2$ on the day of hCG injection, the mean number of oocytes retrieved, total motile sperm count, fertilization rate and the mean number of embryos transferred between bHTF (without amino acids) and mHTF (with amino acids) groups. However, total ampules of gonadotropins were higher (p<0.01) in mHTF group than bHTF group. Significantly (p<0.05) more clinical pregnancies were recorded in mHTF group (13/30) compared with bHTF group (9/46). The multiple pregnancy rates were 11.1% in bHTF group and 7.7% in mHTF group. There were one ectopic pregnancy in mHTF group and one heterotopic pregnancy in bHTF group. Abortion rates were 22.2% in bHTF group and 7.7% in mHTF, respectively. The ongoing pregnancy or livebirth rate was significantly (p<0.05) higher in mHTF group (12/30) than bHTF group (7/46). These results suggest that the addition of amino acids in culture media is essential for culture of zygotes in vitro and adjustment of energy substrates in phosphate-free culture media appears to be beneficial for human IVF-ET procedure.

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자궁내막증이 있는 불임 여성에서 중등도에 따른 체외 수정의 결과 비교 (Comparison of IVF Outcomes in Patients with Endometriosis According to Severity)

  • 김혜옥;강인수
    • Clinical and Experimental Reproductive Medicine
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    • 제33권4호
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    • pp.219-227
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    • 2006
  • 목 적: 자궁내막증이 체외 수정에 미치는 영향에 대하여 알아보고, 자궁내막증의 체외 수정 결과의 차이에 대해 살펴보고자 하였다. 연구방법: 1994년부터 2004년까지 제일병원 아이소망센타에서 자궁내막증으로 체외 수정을 시술 받은 697명의 환자 (총 1,199주기)를 후향적으로 연구하였다. 경증의 자궁내막증은 638주기, 중증의 자궁내막증은 561주기였으며, 난관 요인을 가진 325명 (459주기)를 대조군으로 하였다. 제외 기준으로는 여성의 나이가 35세 이상, basal FSH level이 20 mIU/ml 이상인 경우, 심각한 남성 요인의 경우를 제외하였다. 결 과: 중증의 자궁내막증은 난관 요인 보다 획득된 난자의 수 ($9.97{\pm}7.2$ vs. $13.4{\pm}7.9$ (p<0.0001)), 총 배아 수 ($6.5{\pm}4.8$ vs. $9.1{\pm}5.6$ (p<0.0001)), 양질의 배아 수 ($2.43{\pm}1.6$ vs. $2.74{\pm}1.7$ (p=0.013))가 통계적으로 유의하게 낮았다. 하지만, 중증의 자궁내막증의 임신율은 난관 요인과 유사하였다 (35.7 vs. 36.8 (%)). 경증의 자궁내막증은 중증의 자궁내막증과 난관 요인보다 불임 기간이 길었으며 ($55.4{\pm}25.7$ vs. $47.6{\pm}25.6$ vs. $44.4{\pm}30.9$ (개월) p<0.0001)), 수정률이 의미 있게 낮았으나 ($64.8{\pm}22.9$ vs. $69.9{\pm}22.5$ vs.$70.8{\pm}20.8$ (%) (p<0.0001)), 임신율에 유의한 차이는 없었다 (31.1 vs. 35.7 vs. 36.8 (%)). 또한, 체외 수성 이전에 치료 받은 병력이 있던 경증과 중증의 자궁내막증 (363주기 vs. 470주기)은 경증의 자궁내막증에서 중증의 자궁내막증보다 불임 기간이 길고 ($56.5{\pm}26.3$ vs. $46.9{\pm}25.8$ (개월), p<0.0001), 수정률이 낮았으며 ($64.7{\pm}23.3$ vs. $70.5{\pm}22.7$ (%), p=0.001), 임신율과 태아 생존율이 통계적으로 유의하게 낮았다 (29.2 vs. 36.2 (%), p=0.045, 23.9 vs. 31.5 (%), p=0.043). 결 론: 체외 수정 시 이전에 치료를 받았던 경증의 자궁내막증은 중증의 자궁내막증보다 임신율과 태아 생존율이 낮았고, 이는 현저한 수정률 감소와 긴 불임 기간이 관련이 있다고 생각된다. 따라서, 장기간의 불임 기간을 가진 경증의 자궁내막증을 가진 불임 여성은 체외 수정을 좀 더 일찍 고려해 볼 수 있겠다.