In vitro fertilization in unstimulated cycles: a new application

After four unsuccessful attempts at multiple follicular induction with exogenous gonadotropins, a patient underwent two attempts at IVF in spontaneous cycles triggered with hCG. The second attempt resulted in the transfer of three embryos and a successful singleton intrauterine pregnancy. We believe that unstimulated IVF is a viable option for patients with ovulatory cycles. It should be considered in cases of failed hyperstimulation, and may become a primary treatment option in the future.     

In vitro fertilization following natural cycles in poor responders.

This prospective study was designed to examine the feasibility of natural cycle in vitro fertilization (IVF) in poor responders, and the clinical factors that may predict successful outcome. Twenty-two poor responders underwent IVF treatment with 44 unstimulated cycles. The results of the natural cycles were compared with those of the 55 low-response stimulated cycles of these patients during the 12 months prior to the study. Eighteen (82%) patients had at least one oocyte retrieved, while nine (41%) had at least one cycle with embryo transfer. Two (9%) patients each gave birth to a healthy term baby. These results are comparable with those of the stimulated cycles. Serum early follicular follicle stimulating hormone (FSH) level was found to be the only reliable predictor of oocyte recovery and overall outcome in each specific natural cycle. However, because of great variability in basal FSH levels among different cycles of the same patient, this is not a reliable predictor of outcome in future cycles. We conclude that poor responders are a unique group of patients who may benefit from natural-cycle IVF treatment.     

无刺激周期未成熟卵母细胞体外培养用于多囊卵巢综合征不孕患者治疗的临床观察

目的探讨无刺激周期未成熟卵母细胞体外培养在治疗多囊卵巢综合征(PCOS)不孕患者的应用价值。方法对70例PCOS患者,在人工周期或自然周期第10～12天行阴道B超监测,如双侧卵巢中无直径>8mm的卵泡,即肌内注射人绒毛膜促性腺激素10000IU,36h后经阴道穿刺取卵,将取出的未成熟卵母细胞进行体外成熟及体外受精胚胎移植。结果共进行体外成熟周期94个,移植周期75个。共获得卵母细胞1283个,获得成熟838个(65.3%,838/1283),其中受精553个(66.0%,553/838),获得胚胎402个(48.0%,402/838),获得优质胚胎199个(23.7%,199/838)。生发泡期卵母细胞的成熟率、受精率、获得胚胎率及优质胚胎率,分别为67.7%、66.4%、47.6%及24.1%;第1次减数分裂中期的卵母细胞,分别为69.7%、71.7%、52.2%及26.1%,生发泡期与第1次减数分裂中期比较,差异均无统计学意义(P>0.05)。无法评价的卵母细胞的成熟率、受精率、获得胚胎率及优质胚胎率,分别为44.8%、53.8%、46.2%及16.9%,与生发泡期及第1次减数分裂中期比较,差异均有统计学意义(P<0.05)。75个移植周期中,18例获得临床妊娠,妊娠率为24%(18/75)。结论无刺激周期未成熟卵母细胞体外成熟及体外受精胚胎移植可用于PCOS不孕患者的治疗,并能取得一定的妊娠成功率。     

In vitro fertilization in spontaneous cycles--our experience

OBJECTIVE: To study the efficacy of a simple protocol of natural cycle in vitro fertilization. METHOD: A retrospective study of 59 natural treatment cycles in 37 infertile couples with previous unsuccessful attempts of conventional in vitro fertilization. RESULTS: In 24% of cycles, the aspiration was cancelled because of inadequate visualization of follicles or because of preterm ovulation. Aspiration was performed in 45 cycles with oocyte retrieval of 82% per aspiration. Embryo transfer was performed in 30 cycles, pregnancy rate per pick-up was 15%. CONCLUSION: In vitro fertilization in a natural cycle is a simple, relatively cheap and comfortable procedure with reasonable results and can be offered to patients scheduled not only for in vitro fertilization because of tubal factor but also to patients with endometriosis or unexplained infertility.     

Extraperitoneal laparoscopic lymph node staging: the University of Southern California experience

OBJECTIVES: To describe our experience with extraperitoneal lymph node staging in gynecologic oncology. MATERIALS AND METHODS: The extraperitoneal approach was performed to assess the lymph node histology in patients with gynecologic malignancies. The nodes are approached from a lateral approach after dissecting open the extraperitoneal space bluntly and with insufflation. Bilateral aortic nodes are taken from a left-sided or right-sided approach depending on the patient's characteristics. RESULTS: Forty-six patients underwent this procedure over a 2.5-year period. Thirty-seven patients had cervical cancer. The median BMI was 27.1 (17.7-38.1). The median lymph node yield was 14 (0-60). Two patients had disruption of the peritoneum such that the aortic lymphadenectomy had to be completed transperitoneally. No patients required laparotomy. No patients required transfusion. DISCUSSION: This technique permits histologic evaluation of the retroperitoneal nodes with minimal risk of intraabdominal adhesions. Recovery is rapid and further therapy can be prescribed shortly. The data on the nodes can assist in treatment planning.     

In vitro fertilization and embryo transfer: two-year experience

Between February 1983 and January 1985, 206 laparoscopies were performed on 172 women following controlled ovarian hyperstimulation with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Sixty-four clinical pregnancies advanced beyond the sixth week of gestation and were confirmed by ultrasound; and 37.2% of the patients conceived after in vitro fertilization and embryo transfer. The clinical pregnancy rate was 31.1% when based on the number of laparoscopies performed and 33.9% when based on the number of embryo transfers. There were 12 multiple pregnancies (18.8%), 11 miscarriages (17.2%), and one ectopic (tubal) pregnancy (1.6%). The most important factors contributing toward the success of this program were the establishment of specific criteria for patient selection, rigid adherence to clinical and laboratory protocols, and the maintenance of strict quality control.     

In vitro fertilization and embryo transfer during natural cycles

OBJECTIVE: To report the results of in vitro fertilization and embryo transfer (IVF/ET) performed during natural cycles. STUDY DESIGN: A prospective clinical study. RESULTS: Thirty-two cycles were started in 19 patients who had regular ovulatory cycles and tubal factors or unexplained infertility only as the cause of infertility. Egg collection was performed in 12 cycles, and four pregnancies resulted from ET in eight cycles. The pregnancy rates were 12.5% per cycle initiated, 33.3% per retrieval cycle and 50% per transfer. CONCLUSION: Natural cycle IVF/ET offers a low-cost alternative to patients with infertility.     

Three protocols for monitoring follicle development in 587 unstimulated cycles of in vitro fertilization and intracytoplasmic sperm injection. A comparison.

OBJECTIVE: To test the adequacy of unstimulated cycles for intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) and to evaluate implantation and pregnancy rates in three monitoring protocols. STUDY DESIGN: A retrospective chart review of 587 patients undergoing IVF and ICSI in unstimulated cycles was performed. In the first group (protocol A), all cycles were monitored by ultrasound only. Human chorionic gonadotropin (hCG) was given when the mean follicle diameter reached 18 mm. In protocol B, hCG was given when serum estradiol (E2) or follicle diameter reached the critical value (0.91 nmol/L and 18 mm). With a smaller follicle diameter, the E2 level had to be higher, and vice versa. In protocol C, hCG was administered when the serum E2 was > 0.49 nmol/L and follicle diameter at least 15 mm. Cycles with positive luteinizing hormone in urine before hCG was given were cancelled. RESULTS: The cancellation rate was lower in protocol C (33/335, 9.8%) than protocol B (42/151, 27.8%) and A (41/101, 40.5%). In protocol C the pregnancy rate per cycle was higher with IVF (n = 219) and ICSI (n = 116) cycles (10.5% and 12.1%) than when protocol B was used (3.8% and 4.3%). The pregnancy rate per transfer was highest when protocol C was used in the IVF (23/105, 21.9%) and ICSI group (14/53, 26.4%). CONCLUSION: Unstimulated cycles monitored by serum E2, urinary luteinizing hormone and ultrasound can produce an acceptable pregnancy rate after IVF and ICSI.     

未经促排卵的未成熟卵母细胞行体外成熟治疗不孕症的临床研究

目的探讨未经任何药物刺激的未成熟卵母细胞行体外成熟（IVM）治疗不孕症的临床价值。方法40例不孕患者接受54个IVM周期,其中多囊卵巢综合征（PCOS）不孕患者26例,经其他辅助生育技术失败14例。在未采用任何药物刺激的前提下,于月经周期的第9—12天,在超声引导下经阴道对两侧卵巢内直径≤10mm的卵泡进行穿刺取卵。对取出卵母细胞于体外培养24～48h,待第一极体出现后,进行卵母细胞质内单精于注射（ICSI）,18h后观察受精情况,继续培养24—48h,直至胚胎移植,移植前行激光辅助胚胎孵化。结果54个IVM周期中,有7个周期取消,取消率为13％;共移植周期47个,共获得未成熟卵母细胞857个,平均每周期18．2个。体外培养48h后,卵母细胞成熟率为73．7％（632／857）,正常受精率为75．3％（476／632）,卵裂率为91．2％（434／476）。移植日子宫内膜厚度平均为8．9mm,平均移植胚胎4．3个（2—6个）;1例生化妊娠,19例临床妊娠,每取卵周期的临床妊娠率为35％（19／54）,每移植周期的临床妊娠率为40％（19／47）。26例PCOS不孕患者共移植周期34个,1例生化妊娠,15例临床妊娠,每移植周期的临床妊娠率为44％（15／34）。结论未经促排卵药物刺激的卵母细胞行IVM用于治疗各种原因的不孕症,尤其是PCOS不孕患者,是一种有效的治疗方法。     

In vitro fertilization program based on programmed cycles monitored by ultrasound only.

OBJECTIVE: Programmed oocyte retrieval was performed in order to make the in vitro fertilization (IVF) program cheaper and work of the IVF team easier. METHOD: In a group of 77 patients included in the IVF program, the menstrual cycle was modified with estrogen-progesterone contraceptive pills. For this reason, it was possible to start the stimulation protocol in all patients on the same day. The stimulation protocol was a combination of clomiphene (100 mg) for 5 days and HMG (150 IU) every other day. Cycles were monitored by ultrasound only. RESULT: The implantation rate per embryo transfer was 22.4%. The number of embryos per embryo transfer was low (2.6 +/- 1.4) and eliminated the need for cryopreservation. Fertilization rate (82%) and embryo transfer rate (87%) were high. The take home baby rate was 14.3%. CONCLUSION: Seventy percent of all punctures were performed in 3 days in the middle of the week. In our conditions, programmed oocyte retrieval is associated with significant economic benefits.     

The significance of elevated early follicular-phase follicle stimulating hormone (FSH) levels: Observations in unstimulated in vitro fertilization cycles

Objective: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles. Study Design: We compared cycles with elevated day 3 FSH levels (>20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels. Patients: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH. Results: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E₂) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies. Conclusions: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.     

In vitro fertilization without ovarian stimulation: a simplified protocol applied in 80 cycles

Ovulation induction with various hormonal agents has become a standard component of in vitro fertilization (IVF) cycles to obtain multiple oocytes. Failure to anticipate the retrieval of more than two oocytes often results in cancellation of the cycle. In this study, we report our results in 80 unstimulated IVF cycles. Serum estradiol (E2) and pelvic ultra-sound monitoring were begun on day 9 of the cycle. Human chorionic gonadotropin (hCG) was administered when the E2 level exceeded 180 pg/mL and the dominant follicle was greater than 18 mm. Eighteen pregnancies were obtained (22.5%/cycle), and 14 (17.5%/cycle) are ongoing. We conclude that favorable results can be obtained from unstimulated IVF cycles, despite replacement of a single embryo.     

Addition of a gonadotropin releasing hormone (GnRH) antagonist and exogenous gonadotropins to unstimulated in vitro fertilization (IVF) cycles: Physiologic observations and preliminary experience

Purpose To describe our preliminary experience with the addition of a GnRH antagonist (Nal-Glu) and exogenous gonadotropins (follicle stimulating hormone; FSH) to unstimulated IVF cycles.Method Seven spontaneously ovulatory women underwent eight unstimulated IVF cycles at our institution. They were treated with a single dose of Nal-Glu, 50 g/ kg, or with a combination of Nal-Glu, 50 g/kg, and exogenous FSH, 150–300 IU, during the late follicular phase of spontaneous cycles. They then received 10,000 IU of human chorionic gonadotropin (hCG) to time accurately follicle aspiration in unstimulated IVF cycles.Results Two women underwent three cycles with Nal-Glu alone on the day of hCG administration. One pregnancy resulted. Five women underwent five cycles with 3 to 6 days of daily Nal-Glu and FSH. Four of these cycles resulted in aspiration after the FSH dose was increased to 300 IU. Nal-Glu and FSH allowed continued development of the dominant follicle without the occurrence of luteinizing hormone (LH) surge.Conclusions (1) Nal-Glu alone given 18 hr prior to hCG did not interfere with continued follicle viability or with the attainment of pregnancy. (2) Simultaneous Nal-Glu and FSH allowed for continued growth and development of the dominant follicle without the occurrence of an LH surge. (3) This preliminary experience confirms the feasibility of this novel approach, which may ultimately enhance the efficacy of unstimulated IVF cycles by eliminating premature ovulation and maximizing control of gonadotropin delivery to the developing follicle.Presented at the 39th Meeting of The Society for Gynecologic Investigation, San Antonio, Texas, March 18–21, 1992.     

卵巢低反应者应用自然周期方案体外受精-胚胎移植的价值

目的探讨自然周期方案行体外受精-胚胎移植(IVF-ET)在卵巢低反应患者的应用。方法对南京大学医学院附属鼓楼医院生殖医学中心2003年11月至2007年7月20例卵巢低反应患者采用自然周期方案进行IVF-ET的临床资料进行回顾性分析。结果20例患者共进行41个起始周期。其中11个周期取消,取消率为26.8%。30个取卵周期中27个周期获得卵子,取卵周期获卵率为90.0%。19个周期进行胚胎移植,起始周期移植胚胎率46.3%,取卵周期移植胚胎率63.3%。临床妊娠6例,其中5例已经分娩,1例流产。移植周期临床妊娠率为31.6%,移植周期分娩率为26.3%。结论自然周期方案行IVF-ET对于卵巢低反应患者是一种简单有效的治疗方法。     

Outcomes of 1503 cycles of modified natural cycle in vitro fertilization: a single-institution experience

PurposeA retrospective cohort study was conducted in a single academic center to determine if modified natural cycle in vitro fertilization (mnIVF) is an acceptable treatment for the infertile couple.MethodsCycles performed between July 2005 and December 2011 were included. In our center’s mnIVF protocol, a GnRH antagonist, gonadotrophin, as well as Indocid are given on a daily basis from detection of a dominant follicle until ovulation induction. The primary outcomes were clinical pregnancy rates (CPR) per cycle started and per embryo transfer (ET). Outcomes were stratified by female patient age (≤35 years and ≥36 years). They were further stratified in each age group by ovarian response status according to the 2011 Bologna criteria.ResultsA total of 1503 cycles of mnIVF, performed in 782 patients, were analyzed. CPRs were 13.7 % per started cycle and 32.5 % per ET. Stratification by ovarian response status (normal or poor) in each age group showed similar CPRs in patients ≤35 years (p = 0.373), and divergent CPRs per ET in patients ≥36 years old (26.26 vs 6.25 %).ConclusionMnIVF is an acceptable treatment option for patients considering IVF, particularly for women ≤35 years old and for women ≥36 years old with normal ovarian response.     

Corpus luteum function in successful in vitro fertilization cycles.

The function of the corpus luteum in early pregnancy has been subject to some controversy. The purpose of our study was to determine the life span of the corpus luteum in early pregnancy after successful GnRH-a/hMG stimulation in IVF-ET. The study consisted of a retrospective analysis of patients after 12 successful singleton intrauterine IVF-ET cycles. Serum samples were obtained during early pregnancy beginning 14 days after hCG administration. The levels of 17 alpha-OHP, hCG, P, and E2 were measured in each sample. A significant negative correlation was noted between 17 alpha-OHP and date from hCG. The x-intercept of the regression line allowed estimation of the life span of the corpus luteum to be 72 +/- 25 days. In conclusion, in GnRH-a/hMG-stimulated IVF-ET cycles that result in a singleton pregnancy, the functional life span of the corpus luteum averages 72 days.     

Establishment of a nonanonymous donor oocyte program: preliminary experience at the University of Southern California

Transvaginal ultrasound-directed oocyte retrieval was performed on eight women functioning exclusively as gamete donors for 10 patients with ovarian failure. Donors included sisters, personal friends, and compensated participants selected by the recipient couple. Oocyte donors underwent controlled ovarian hyperstimulation and transvaginal oocyte aspiration. Thirteen initiated cycles resulted in 11 embryo transfers and six ongoing pregnancies. There were no complications, and all donors stated a willingness to undergo the procedure again. The use of nonanonymous oocyte donation appears both efficacious and efficient and is recommended as an option for achieving pregnancy in women with ovarian failure.