FEMALE INFERTILITY: IVF Clinical

J Obstet Gynecol Reprod Biol 2002 May 10;102(2):184-7
In vitro fertilization in spontaneous cycles--our experience. Bauman R, Mihaljevic D, Kupesic S, Kurjak A.
Opca bolnica Sveti Duh, Klinika za ginekologiju i porodnistvo, Sveti Duh 64, 10000 Zagreb, Croatia. renato.bauman@zg.hinet.hr
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.

Hum Reprod 2002 Jan;17(1):213-8
Concentration of leukaemia inhibitory factor (LIF) in uterine flushing fluid is highly predictive of embryo implantation.
Ledee-Bataille N, Lapree-Delage G, Taupin JL, Dubanchet S, Frydman R, Chaouat G.
INSERM U131, Clamart, France. Ledeenathalie@aol.com
BACKGROUND: There is strong evidence that locally secreted cytokines control the implantation process and can cause implantation failure. Uterine flushing fluids were analysed to determine their concentrations of leukaemia inhibitory factor (LIF) and tumour necrosis factor (TNF). METHODS AND RESULTS: We began by flushing the uterine cavities of 33 infertile patients on day 26 of two consecutive cycles. The concentrations of LIF (by enzyme-linked immunosorbent assay) and TNF (by bioassay) were significantly correlated during these cycles (r = 0.762, P = 0.0001 and r = 0.822, P = 0.001 respectively) and hence reliable. Then, after a reference flushing of 30 infertile patients, we followed the outcome of their first consecutive cycle of ovarian stimulation, which preceded either IVF or intrauterine insemination. A total of 10 patients became pregnant. The median concentration of LIF was 0 pg/ml (range: 0-177) and of TNF was 0 U/ml (range: 0-6.17) among those who became pregnant, and 203 pg/ml (range: 0-1620) and 2.14 U/ml (range: 0-16) respectively among those who did not. The LIF concentration was significantly lower in the pregnant group (P = 0.0013). CONCLUSION: A low concentration of LIF in the uterine flushing fluid at day 26 was predictive of subsequent implantation. Use of this procedure should increase the number of IVF attempts yielding successful pregnancies and also lead to corrective therapies.

Hum Reprod 2002 Jan;17(1):137-8
Acute ureteral obstruction following transvaginal oocyte retrieval for IVF. Miller PB, Price T, Nichols JE Jr, Hill L
Center for Women's Medicine, Division of Reproductive Endocrinology and Infertility, Greenville, South
Carolina, USA. pmiller@ghs.org
Transvaginal, ultrasound-guided oocyte retrieval has become the gold standard for IVF therapy. Despite a low reported complication rate, here a case is reported of acute ureteral obstruction following seemingly uncomplicated oocyte retrieval. Prompt diagnosis and ureteral stenting led to rapid patient recovery with no long-term urinary tract sequelae. Ureteral injury needs to be included in the differential diagnosis of a patient presenting with pelvic/abdominal pain following oocyte retrieval.

Chin Med J (Engl) 1999 Jan;112(1):34-6
Relationship between serum antisperm antibodies and anticardiolipin antibodies and clinical pregnancy outcome in an in vitro fertilization and embryo transfer program. Tian X, Zhang L, Wu Y, Yang C, Liu P.
Department of Obstetrics and Gynecology, Third Clinical Medical School, Beijing Medical University, Beijing 100083, China.
OBJECTIVE: To study the influence of maternal immunological factors on clinical pregnancy outcome in an in vitro fertilization and embryo transfer (IVF-ET) program. METHODS: One hundred and fifty IVF-ET treatment cycles from November 1995 to November 1996 were studied. The indication for IVF-ET treatment was bilateral blocked tubes. Serum antisperm antibodies and anticardiolipin antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Cleavage rate and successful pregnancy rate in relation to antibody status of infertile women after IVF-ET treatment were assessed. RESULTS: Lower cleavage rate (64.2% +/- 32.1%) was found in 44 cycles of antisperm antibody seropositive women, compared with 84.8% +/- 18.7% in 106 cycles of seronegative women (P < 0.05). The clinical pregnancy rate was 31.8% in antisperm antibody-positive cycles and 20.8% in negative cycles (P > 0.05). The abortion rates of the two groups were similar (P > 0.05). Lower pregnancy rate (9.5%) was found in 21 cycles of serum anticardiolipin antibody-positive group, compared with 26.3% in 129 cycles of seronegative women (P < 0.05). Of patients with bio-chemical pregnancy and no pregnancy, 20.0% and 16.2%, respectively, had seropositive anticardiolipin antibody, compared with 5.6% of patients with clinical pregnancy (P < 0.05). CONCLUSION: Serum immunological factors may play a part in clinical pregnancy outcome in IVF-ET.

Hum Cell 2001 Jun;14(2):135-40
Embryo transfer after autologous endometrial coculture improves pregnancy rates. Seta M.
Since the first in-vitro fertilization (IVF) baby born in 1978, the technique of in-vitro fertilization-embryo transfer (IVF-ET) has been well established and widely used by clinicians all over the world. However, the success rate of IVF-ET still remains relatively low. Sub-optimal embryo culture condition may consider as a factor contribute to the poor success rate. Autologous endometrial coculture is a newly developed technique able to enhance development of fertilized eggs using the patient's own endometrial cells. A clinical tryout was conducted in our institute. Patients underwent either classic IVF (n = 82) (i.e., control group) or autologous endometrial coculture (n = 134) (i.e., coculture group). The clinical pregnancy rate (per patient) was significantly higher in coculture group (48.5%) than control group (24.3%). Patients were further subgrouped according to their age. For each subgroup, the clinical pregnancy rates were again consistently higher and the miscarriage rates were consistently lower in the coculture group than in the control groups. Coculture also increased clinical pregnancy rate of patients who failed IVF at least twice from 0% to 26.6%. Our data confirmed that autologous endometrial coculture is an effective method to improve the success rate of IVF-ET. The evidence of improving clinical pregnancy rates and reducing abortion rates after coculture suggest that coculture indeed improved success rates by improving embryo quality.

Curr Womens Health Rep 2001 Oct;1(2):152-6
Cryopreservation of ovarian tissue: banking reproductive potential for the future. Lee D, Ouhibi N, Battaglia D.
Division of Reproductive Endocrinology and Infertility, University Fertility Consultants, 1750 SW Harbor
Way, Portland, OR 97201-5133, USA. leedavi@ohsu.edu Cryopreservation of ovarian tissue is a technology that holds promise for banking reproductive potential for the future. It may be apropos for cancer survivors who have undergone treatment with sterility-inducing chemotherapy. Although there is some evidence suggesting cellular and molecular injury with the freezing and thawing process, there are examples in both animals and humans that transplantation of cryopreserved ovarian tissue can effectively bank reproductive potential for the future. This technology may ultimately have applications for in vitro fertilization, and preventing natural or iatrogenic menopause.

Curr Opin Obstet Gynecol 2002 Jun;14(3):275-81
Poor responders: does the protocol make a difference? Mahutte NG, Arici A.
Department of Obstetrics and Gynecology, Yale University, New Haven, Connecticut 06520-8063, USA. An inadequate response to gonadotropins during in-vitro fertilization treatment may result in cycle cancellation, fewer embryos available for transfer and decreased pregnancy rates. For these reasons, numerous strategies to improve ovarian stimulation in poor responders have been proposed. These include variations in the type, dose and timing of gonadotropins, gonadotropin-releasing hormone agonists and gonadotropin-releasing hormone antagonists. Unfortunately, despite optimism generated by studies using retrospective controls, epidemiologically sound trials have been scarce. Indeed, of the three prospective randomized trials performed in poor responders to date no compelling advantage for one stimulation protocol over another has been established. Although this lack of improvement may reflect inadequate sample sizes, an alternative explanation is simply that the protocol, after a certain point, does not make a difference. Aside from oocyte donation, greater hope for poor responders may rest in aneuploidy screening, in-vitro oocyte maturation and cytoplasm/nuclear transfer.

Ultrasound Obstet Gynecol 2002 May;19(5):484-9
Evaluation of cycle-to-cycle variation of endometrial responsiveness using transvaginal sonography in women undergoing assisted reproduction.
Basir GS, O WS, So WW, Ng EH, Ho PC.
Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong. gsbasir@hotmail.com
OBJECTIVES: To investigate the variation of endometrial responsiveness between cycles within the same women undergoing assisted reproduction. METHODS: The sonographic endometrial thickness in ovarian stimulation cycles was compared with that of subsequent natural cycles. One hundred and thirty-six ovarian stimulation cycles of in-vitro fertilization and embryo transfer were evaluated. Women who did not conceive in in-vitro fertilization cycles were subsequently seen in natural cycles (n = 97) or the next in-vitro fertilization cycle (n = 39). Based on a receiver-operating characteristics (ROC) curve using endometrial thickness to predict pregnancy, the first in-vitro fertilization cycles were classified according to the endometrial thickness as optimal (> 8 mm) in 98 cycles, or suboptimal (< or = 8 mm) in 29 cycles. Similarly, spontaneous cycles were classified as suboptimal (< or = 7 mm) in 28 cycles and optimal (> 7 mm) in 69 cycles. RESULTS: The pregnancy rates were significantly lower (P < 0.05; Fisher's Exact test) in the suboptimal group in both the in-vitro fertilization and frozen embryo transfer cycles. There was a strong correlation (r2 = 0.745) and a significant difference (P < 0.001; Wilcoxon signed rank sum test) between the endometrial thickness of stimulation and natural cycles. CONCLUSION: It is possible to predict the occurrence of optimal or suboptimal endometrial response in natural cycles of women, after evaluation in stimulated cycles, with a high degree of reliability. Risk of implantation failure can be identified before subsequent treatment cycles and adjuvant therapeutic strategies may be planned to improve the endometrial response before embryo transfer.

Hum Reprod 2002 Feb;17(2):351-6
Fluid accumulation within the uterine cavity reduces pregnancy rates in women undergoing IVF. Chien LW, Au HK, Xiao J, Tzeng CR.
Department of Obstetrics and Gynaecology, Taipei Medical University Hospital, Taipei, Taiwan.
BACKGROUND: The occurrence of fluid accumulation within the uterine cavity was examined in women undergoing IVF to investigate its correlation with tubal disease and impact on the pregnancy outcome. METHODS: A registry of ultrasound procedures spanning 5 years was retrospectively studied. RESULTS: Thirty five out of 746 (4.7%) IVF cycles were identified as having uterine fluid accumulation, and 15 (2.0%) persisted until the day of embryo transfer. Two of the 20 cycles of women with transient fluid accumulation were pregnant, and none of those with fluid retention on the day of embryo transfer conceived. The pregnancy rate was only 5.7% (2/35) in women with uterine fluid accumulation detected during IVF cycles. In contrast, the pregnancy rate was 27.1% (193/711) among women in whose cycles no fluid accumulation was detected (P = 0.0048). Uterine fluid accumulation during IVF cycles was found in 8% (18/225) of women documented with tubal factor compared with 3.3% (17/521) with non-tubal factor (P = 0.005). CONCLUSIONS: Fluid accumulation within the uterine cavity during the IVF transfer treatment could be observed in patients with both tubal and non-tubal factors; however, it mainly occurred in women with tubal infertility. Although it is not a common complication of IVF cycles, excessive uterine fluid is detrimental to embryo implantation.

Hum Reprod 2001 Aug;16(8):1698-9
The development of an oocyte-containing follicle during gonadotrophin-releasing hormone agonist administration.
Almagor M, Hovav Y.
IVF and Fertility Laboratory, Department of Obstetrics and Gynecology, Bikur Cholim Hospital, 5 Strauss St., Jerusalem 91004, Israel. almagors@hotmail.com Administration of gonadotrophin-releasing hormone (GnRH) agonist in a 29 year old woman with infertility due to ovulatory dysfunction resulted in the development of several ovarian cysts. After human chorionic gonadotrophin (HCG) was injected, the cysts were aspirated and one mature oocyte was retrieved. Intracytoplasmic sperm injection (ICSI) was performed and the resulting embryo was transferred. A singleton pregnancy was obtained and a healthy baby was born at 36 weeks of gestation. Because GnRH agonist-derived cysts may contain oocytes, we suggest that when the growth of cysts is accompanied by high concentrations of oestradiol, the administration of HCG may be useful to achieve oocyte maturation and advance IVF treatment.

Int J Fertil Womens Med 2001 May-Jun;46(3):145-50
Laparoscopic Fertility-Promoting Procedures of the fallopian tube and the uterus. Sammour A, Tulandi T.
Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada. Assisted reproductive technology and reproductive surgery can be complementary, and the feasibility of laparoscopic suturing has facilitated conducting reproductive surgery entirely by laparoscopy. Young women with tubal disease can be offered surgery, whereas older women, with their rapid decline in fertility, are better treated with in vitro fertilization (IVF). IVF should be the first line of treatment for women with a severe degree of hydrosalpinx, or with extensive and dense adhesions. However, the presence of hydrosalpinx decreases IVF pregnancy rates. In those whose hydrosalpinx is seen on ultrasound, especially after failed IVF cycles, a laparoscopic salpingectomy can be done. For tubal anastomosis, the superior results of this procedure are well established. The association between uterine myoma and infertility is unclear. However, in those with a distorted uterine cavity, and no other cause of infertility, myomectomy can be considered; myomectomy can be done by laparoscopy. Because of the risks of uterine rupture, proper closure of the uterine incision is of utmost importance.

J Ultrasound Med 2001 Aug;20(8):869-75
Sonographic diagnosis of pelvic adhesions in patients after ovum pickup. Shalev J, Mashiach R, Fisch B, Royburt M, Bar-Hava I, Krissi H, Meizner I.
Ultrasound Unit, Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva, Israel. OBJECTIVE: To evaluate the use of transvaginal sonography for the detection of pelvic adhesions by using clear free fluid in the pouch of Douglas found after ovum pickup. METHODS: A prospective clinical study was performed in an infertility unit of an academic research facility. Sonography was performed in 50 women with infertility 3 days after ovum pickup, and the visceral peritoneum of the uterus, the ovaries, and the fallopian tubes was scanned for possible pelvic adhesions. RESULTS: The serosal surfaces of the uterus, ovaries, and fallopian tubes were successfully observed for the presence of adhesions in 86%, 68%, and 20% of the patients, respectively. Improved visualization was associated with an increased amount of pelvic fluid for the uterus (P = .01) but not for the ovaries and fallopian tubes. The amount of fluid in the pelvis correlated with an increased number of retrieved oocytes (P = .07) and a decreased need for manual manipulation to achieve proper imaging of the uterus (P = .001). CONCLUSION: Transvaginal sonography performed in the presence of fluid in the pelvis may show adhesions mainly attached to the uterus and ovaries. Assessment of possible mechanical factors is important in planning treatment of patients with infertility.

Fertil Steril 2002 Aug;78(2):245-51
Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer. Chien LW, Au HK, Chen PL, Xiao J,
Tzeng CR.
Department of Obstetrics and Gynecology, Taipei Medical University and Hospital, Taipei, Taiwan.
OBJECTIVE: To investigate the correlation of blood flow detected by color Doppler sonography in the endometrial-subendometrial unit with pregnancy outcome of IVF-ET treatments. DESIGN: Prospective clinical study. SETTING: University setting. PATIENT(S): Six hundred twenty-three patients selected prospectively on the day of ET. INTERVENTION(S): Transvaginal ultrasound examination was performed before ET. MAIN OUTCOME MEASURE(S): Association between pregnancy outcome and distribution of endometrial-subendometrial blood flow (primary outcome measure) and between pregnancy rate and endometrial measurements as well as uterine arterial blood flow (secondary outcome measures). RESULT(S): The overall pregnancy rate was 28.4% (177/623) per ET. The pregnancy and implantation rates of patients with the presence of both endometrial and subendometrial flow were 47.8% (64/134) and 24.2% (94/388); for patients with subendometrial flow only, 29.7% (102/343) and 15.8% (153/967); and for patients with no detectable endometrial-subendometrial flow, 7.5% (11/146) and 3.5% (13/376), respectively. The presence of both endometrial and subendometrial blood flow is indicative of good endometrial receptivity, whereas the absence of both represents a poor uterine environment. Nondetectable endometrial-subendometrial flow was associated with women who were older, had a thinner endometrium, and had higher uterine arterial resistance compared with those women who had detectable flow. CONCLUSION(S): Endometrial-subendometrial blood flow distribution pattern assessed by transvaginal color Doppler before ET is correlated with the implantation and pregnancy rate of IVF treatment.

Hum Reprod 2002 Nov;17(11):2885-2890
The usefulness of ultrasound guidance in frozen-thawed embryo transfer: a prospective randomized clinical trial.
Coroleu B, Barri PN, Carreras O, Martinez F, Veiga A, Balasch J.
Service of Reproductive Medicine, Department of Obstetrics and Gynaecology, Institut Universitari Dexeus, Barcelona and Institut Clinic of Gynaecology, Obstetrics and Neonatology, Faculty of Medicine-University of Barcelona, Hospital Clinic-Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
BACKGROUND: Recent randomized controlled trials have shown that implantation and pregnancy rates were improved with ultrasound-guided embryo transfer compared with clinical touch in fresh IVF cycles associated with supraphysiological ovarian steroid levels. However, the usefulness of ultrasound guidance in frozen-thawed embryo transfer where potential hormonal influences are lacking has not been appropriately investigated. METHODS: A total of 184 consecutive patients undergoing thawed embryo transfer cycles with hormone replacement under pituitary suppression were randomized by computer-generated randomization table to two study groups: 93 had ultrasound-guided (group 1) and 91 had clinical touch (group 2) embryo transfer. RESULTS: There was equal distribution between the two study groups with respect to the main demographic and baseline characteristics of the patients as well as the characteristics of both prior IVF cycles from which embryos were generated and cryopreserved-thawed embryo transfer cycles. However, both pregnancy and implantation rates in group 1 (34.4 and 19.8% respectively) were significantly higher than the corresponding values (19.7 and 11.9%) in group 2. CONCLUSIONS: Ultrasound guidance in frozen-thawed embryo transfer significantly increases pregnancy and implantation rates.

Di Yi Jun Yi Da Xue Xue Bao 2001;21(11):862-864
Study on embryo morphology and clinical result of intracytoplasmic sperm injection for infertility. Huang MZ, Chen SL, Xing FQ.
Center for Assisted Reproduction, Department of Obstetrics and Gynecology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.
OBJECTIVE: To explore the relevance of the embryo morphology with the clinical result of intracytoplasmic sperm injection (ISCI) for infertility treatment. METHODS: A retrospective analysis was conducted of 291 ISCI and 352 in vitro fertility (IVF) cycles collected during the period from January, 1999 to March, 2001. RESULTS: Significant difference was not found in the fertility rates between the 2 groups (75.7% vs 73.2%, P=0.5738), nor in the oocyte lysis rates (10.6% vs 7.9%, P=0.238). The rates of the embryos with more than 20% fragments were similar between the 2 groups (41.2% vs 55.8%, P=0.137), but ICSI group had a significantly lower rate of blastocyst formation (43.1% vs 55.8%, P<0.001). The clinical pregnancy rates and miscarriage rates did not vary significantly between the 2 groups (34.7% vs 39.9%, P=0.189; 8.9% vs 13.4%, P=0.079). CONCLUSIONS: ISCI is an effective treatment for male infertility to achieve uneventful clinical pregnancy.

Impact of metformin therapy on ovarian stimulation and outcome in 'coasted' patients with polycystic ovary syndrome undergoing in-vitro fertilization. Stadtmauer LA, Toma SK, Riehl RM, Talbert LM.
Jones Institute for Reproductive Medicine, 601 Colley Avenue, Norfolk, VA 23507, USA; e-mail: Stadtmla@evms.edu
This study was designed to determine if metformin therapy improves ovarian stimulation and IVF outcomes in coasted patients with clomiphene-resistant polycystic ovarian syndrome (PCOS). A retrospective#10; data analysis was performed on women with clomiphene citrate-resistant PCOS treated with or without metformin, who underwent 72 cycles of IVF-embryo transfer with intracytoplasmic sperm injection (ICSI).#10; In 59 cycles, patients were coasted to allow oestradiol concentrations to drop before human chorionic gonadotrophin administration. In patients undergoing coasting, the outcome of IVF with ICSI was compared#10; in those who were treated and untreated. In patients treated with metformin, follicular fluid concentrations of testosterone and insulin were significantly lower (60.5 +/- 5 versus 79.1 +/- 6#10; ng/dl; P < 0.05 and 18 +/- 2.5 versus 22 +/- 2.4 &mgr;IU/ml; P < 0.05 respectively), and the mean number of oocytes retrieved (22.3 +/- 2.4 versus 19.7 +/- 1.6) did not differ.#10; The metformin-treated group showed an increase in the mean number of mature oocytes, oocytes fertilized and cleaving embryos (4-cell or greater by 72 h). However, in the group of patients undergoing coasting,#10; maximum oestradiol concentrations and number of days of coasting were all lower in the metformin-treated group with increased clinical pregnancy rates (71 versus 30%, P < 0.05). Therefore, metformin#10; use appears beneficial in improving IVF outcomes in clomiphene citrate-resistant PCOS patients. #10;

Fertil Steril 2002 Nov;78(5):1068-72
Minimal ovarian hyperstimulation for in vitro fertilization using sequential clomiphene citrate and gonadotropin with or without the addition of a gonadotropin-releasing hormone antagonist. Williams SC, Gibbons WE, Muasher SJ, Oehninger S.
Jones Institute for Reproductive Medicine, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia, USA
OBJECTIVE: To compare the results of a minimal-stimulation protocol with those of a standard protocol used for IVF.DESIGN: Retrospective, controlled study.SETTING: University center.PATIENT(S): Fifty-five patients undergoing IVF using a minimal-stimulation protocol with or without adjuvant therapy with a GnRH antagonist. A control group consisted of age- and diagnosis-matched patients undergoing a standard long GnRH agonist (GnRH-a)-gonadotropin stimulation during the same time period.INTERVENTION(S): Clomiphene citrate and gonadotropins, with or without the GnRH antagonist ganirelix.MAIN OUTCOME MEASURE(S): Oocytes recovered and pregnancy rates.RESULT(S): The number of oocytes retrieved was significantly lower for the minimal-stimulation regimen compared with the case of the long GnRH-a protocol (4.8 +/- 2.6 vs. 16.2 +/- 7.5, respectively). The clinical pregnancy rate per transfer, however, was not significantly different between the two regimens (37% vs. 41%, minimal stimulation vs. long GnRH-a protocol, respectively). The addition of ganirelix resulted in at least the same pregnancy outcome as compared with the case of cycles without the antagonis
CONCLUSION(S): Minimal stimulation using clomiphene citrate followed by gonadotropin for IVF results in pregnancy rates equal to the standard long GnRH-a-gonadotropin protocol. The addition of ganirelix resulted in at least similar results with the advantage of eliminating the occurrence of a premature endogenous LH surge.


Fertil Steril 2002 Nov;78(5):1061-7
Effect of highly purified urinary follicle-stimulating hormone on oocyte and embryo quality. Selman HA, De Santo M, Sterzik K, Coccia E, El-Danasouri I.
Istituto Europeo Medicina della Riproduzione Abruzzese, Spatocco Hospital, Chieti, Italy
OBJECTIVE: To determine the effects of ovarian stimulation with highly purified urofollitropin on oocyte and embryo quality.DESIGN: Parallel randomized open-label clinical study.SETTING: Assisted reproduction centers.PATIENT(S): Two hundred sixty-seven infertile couples undergoing IVF/ICSI.INTERVENTION(S): All participants underwent standard down-regulation with GnRH analogue. One hundred thirty-three participants received highly purified urinary FSH and 134 controls received recombinant FSH.MAIN OUTCOME MEASURE(S): Primary end points were number of morphologically mature oocytes retrieved, embryo quality, and pregnancy and implantation rates. Secondary end points were: total number of days of FSH stimulation, total dose of gonadotropin administered, fertilization rate per number of retrieved oocytes, embryo cleavage rate, live birth and miscarriage rates, endometrial thickness and estradiol level on the day of hCG administration, cancellation rate, and incidence of moderate or severe ovarian hyperstimulation syndrome.RESULT(S): Pregnancy and implantation rates were nonsignificantly higher in the urinary FSH group than the recombinant FSH group (46.5% vs. 36.8% and 22.1% vs. 15.8%, respectively). The grade 1 embryo score was significantly higher in the urinary FSH group than the recombinant FSH (42.1% vs. 33.5%), and the live birth rate was nonsignificantly higher in the former group.CONCLUSION(S): Highly purified urinary FSH is as effective, efficient, and safe for clinical use as recombinant FSH.

Yi Jun Yi Da Xue Xue Bao 2002;22(10):934-6
Interleukin-1beta expression on ovarian granulosa cells and its clinical implication in women undergoing in vitro fertilization. Wang XF, Xing FQ, Chen SL.
Department of Obstetrics and Gynecology, Nanfang Hospital, First Military Medical University, Guangzhou 510515, China.
OBJECTIVE: To detect the expression of interleukin-1beta (IL-1beta) on the surface of human luteinized granulosa cells and to understand its relation to the hormones in human follicular fluid and sera.
METHODS: Thirty-six women receiving in vitro fertilization-embryo transfer (IVF-ET) were enrolled in this study. The luteinizing granulosa cells were recovered from the follicular fluid obtained during transvaginal ultrasound-guided oocyte retrieval for IVF-ET. Flow cytometry was employed to detect the expression of IL-1beta on human granulosa cells, and the concentrations of IL-1beta and the hormones in the follicular fluid were measured by enzyme-linked immunosorbent assay. RESULTS: IL-1beta was detected in the follicular fluid of women with IVT-ET and in the luteinizing granulosa cells. A positive correlation was observed between the sera concentrations of IL-1beta and estradiol on the day when human chorionic gonadotrophin (hCG) was injected (r=0.92, P<0.001), while on the same day the concentration of IL-1beta was shown to be inversely correlated with progesterone levels (r=-0.34, P<0.05). CONCLUSION: IL-1beta in the follicular fluid comes not only from plasma ultrafiltrate but also from luteinizing granulosa cells. The inhibition of progesterone production by luteal cells in the presence of IL-1beta may be one of the factors resulting in the failure of implantation.

Fertil Steril 2002 Oct;78(4):876-8
Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation.
Marconi G, Vilela M, Quintana R, Sueldo C.
OBJECTIVE: To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas. DESIGN: Retrospective study with prospective selection of participants and controls. SETTING: Instituto de Ginecologia y Fertilidad Buenos Aires, Argentina. PATIENT(S): Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle (group A) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility (group B). INTERVENTION(S): Laparoscopic endometrioma cystectomy, IVF-ET cycle. MAIN OUTCOME MEASURE(S): E(2) levels, number of gonadotropin ampoules, follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate. RESULT(S): There were no differences in all the parameters studied (E(2) levels, number of follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation, which was significantly higher in group A than in group B. CONCLUSION(S): Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET.

Fertil Steril 2002 Oct;78(4):757
Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis.
Rickes D, Nickel I, Kropf S, Kleinstein J.
Clinic for Reproductive Medicine and Gynecologic Endocrinology, Faculty of Medicine, Otto-von-Guericke University, Magdeburg, Germany OBJECTIVE: To examine whether ultralong GnRH analog (GnRH-a) therapy after surgical treatment of endometriosis and before ART influences the pregnancy rate.DESIGN: Prospective, randomized, controlled study.SETTING: University clinic for reproductive medicine and gynecologic endocrinology.PATIENT(S): One hundred ten patients with stage II to IV endometriosis according to ASRM criteria.INTERVENTION(S): Fifty-five patients received GnRH-a for 6 months after surgery and subsequently underwent up to 3 cycles of ART, and 55 patients received 3 cycles of ART alone immediately after surgery.MAIN OUTCOME MEASURE(S): Clinical pregnancy rates.RESULTS: The pregnancy rate per patient was higher among patients who received follow-up treatment with GnRH-a. The same results were found in patients with stage III or IV endometriosis who were undergoing IUI or IVF/ICSI.CONCLUSION(S): Ultralong GnRH-a therapy increases the pregnancy rate of ART in patients with severe endometriosis.

Acta Obstet Gynecol Scand 2002 Oct;81(10):954-61
Predictive power of clomiphene citrate challenge test for failure of in vitro fertilization treatment. Csemiczky G, Harlin J, Fried G.
BACKGROUND: To evaluate the impact of ovarian reserve on the outcome of in vitro fertilization (IVF) treatment in 140 women, in a total of 279 treatment cycles. METHODS: All women underwent a clomiphene citrate (CC) challenge test to assess their ovarian reserve before IVF treatment. One hundred and eighteen women (84%) had normal basal follicle stimulating hormone (FSH) levels (3.1-10.0 IU/l) and 22 women (16%) had elevated FSH levels (> 10.0-24.0 IU/l). The FSH levels measured on cycle day 10 showed that 106 (76%) of the women could be regarded as having a normal ovarian reserve and 34 (24%) a diminished ovarian reserve. CONCLUSIONS: We found that the CC challenge test is a useful tool in assessing a woman's ovarian capacity before infertility treatment. The predictive value of the test for a negative outcome of IVF treatment was strong. We recommend performing the test before infertility treatment. This may prevent unnecessary treatment trials and unrealistic expectations from both patients and doctors.

Hum Reprod 2002 Oct;17(10):2700-5
A prospective randomized comparison of sequential versus monoculture systems for in-vitro human blastocyst development.
Macklon NS, Pieters MH, Hassan MA, Jeucken PH, Eijkemans MJ, Fauser BC.
Division of Reproductive Medicine, Department of Obstetrics and Gynaecology and Department of Public Health, Centre for Clinical Decision Sciences, Erasmus Medical Centre, Rotterdam, The Netherlands. BACKGROUND: Extending the period of in-vitro culture to the blastocyst stage may improve implantation rates in IVF treatment. Recognition of the dynamic nature of early embryo metabolism has led to the development of commercially available sequential culture systems. However, their improved efficacy over monoculture systems remains to be demonstrated in prospective studies. METHODS: Embryos obtained from 158 women undergoing IVF treatment were randomized by sealed envelopes to culture in one of three systems: (A) culture for 5 days in our own monoculture medium (Rotterdam medium); (B) culture for 3 days in Rotterdam medium followed by 2 days in fresh Rotterdam medium; (C) culture for 5 days using the commercially available G1/G2 sequential culture system. RESULTS: There were no significant differences in blastulation, implantation or pregnancy rates between the three tested culture systems. CONCLUSION: The employed monoculture system is as effective as the G1/G2 sequential system for the culture of blastocysts for IVF.

Hum Reprod 2002 Oct;17(10):2548-51
Continuation of GnRH agonist administration for 1 week, after hCG injection, prevents ovarian hyperstimulation syndrome following elective cryopreservation of all pronucleate embryos. Endo T, Honnma H, Hayashi T, Chida M, Yamazaki K, Kitajima Y, Azumaguchi A, Kamiya H, Kudo R.
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Department of Obstetrics and Gynecology, Tonan Hospital and Kamiya Lady's Clinic, Sapporo, Japan. BACKGROUND: An approach consisting of elective cryopreservation of all embryos has been proposed for patients at risk of ovarian hyperstimulation syndrome (OHSS). Although elective cryopreservation can prevent pregnancy-induced late OHSS, it cannot prevent early OHSS. Early OHSS is reported to have been complicated with thromboembolism. The study was carried out to assess the efficacy with which the continued administration of GnRH agonist for 1 week after 5000 IU of hCG injection could prevent early OHSS. METHODS: This study employed an open controlled clinical trial at three centres for treatment of infertility in Sapporo. A total of 138 patients at risk of OHSS during IVF-embryo transfer from January 1, 1998 to December 31, 1999, were assigned in turn either to a group with elective cryopreservation of all pronucleate embryos (n = 68) or to one with continuation of GnRH agonist administration for 1 week after hCG injection following elective cryopreservation (n = 70). Subsequently, they were transferred in hormone replacement cycles. The development of severe OHSS (ascites, haemoconcentration) was compared between the two groups. RESULTS: A total of 10% of patients developed severe OHSS necessitating hospitalization because of a marked increase in ascites in the upper abdomen and the haemoconcentration in the elective cryopreservation alone group. On the other hand, none developed severe OHSS in the GnRH agonist continuation group. CONCLUSIONS: In our study, continuation of GnRH agonist for 1 week after hCG injection prevented severe early OHSS following elective cryopreservation of all embryos. This treatment is safe and cost-beneficial, and should be performed promptly for patients at risk of OHSS.

Aust N Z J Obstet Gynaecol 2002 Aug;42(3):285-8
IVF and tubal pathology--not all bad news.
Johnson NP, Sadler L, Merrilees M.
University Division of Obstetrics and Gynaecology, National Women's Hospital, Auckland, New Zealand. OBJECTIVES: In light of evidence that hydrosalpinges compromise the chance of success of in vitro fertilisation (IVF), the aim of this study was to analyse the results of IVF treatment at our clinic in relation to the cause for infertility and to make inferences concerning the impact of mild tubal disease on IVF outcome. CONCLUSION: The overall population of women with tubal disease as the sole cause for infertility (including women with hydrosalpinges and those with non-hydrosalpinx tubal disease) does not have an overall reduced likelihood of success at IVF. This suggests that non-hydrosalpinx tubal disease does not compromise the chance of success from IVF. Surgical treatment prior to IVF for the milder forms of tubal disease is not warranted.

Fertil Steril 2002 Sep;78(3):529-33
Administration of methylprednisolone to prevent severe ovarian hyperstimulation syndrome in patients undergoing in vitro fertilization.
Lainas T, Petsas G, Stavropoulou G, Alexopoulou E, Iliadis G, Minaretzis D.
IVF Unit, Iatriki Erevna, Athens, Greece. iatrikiereyna@ath.forthnet.gr OBJECTIVE: To determine whether administration of methylprednisolone to high-risk women undergoing IVF/ICSI helps reduce the development of OHSS.DESIGN: Retrospective clinical controlled study.SETTING: IVF unit.PATIENT(S): One thousand ten women who underwent IVF/ICSI from January 9, 1997, to December 31, 1999. Ninety-one patients who were at high risk for OHSS were identified by using standard criteria.INTERVENTION(S): Methylprednisolone, 16 mg/d starting on day 6 of the stimulation and tapered after the first pregnancy test (day 13 after embryo transfer).MAIN OUTCOME MEASURE(S): Occurrence of OHSS.RESULT(S): A significantly lower proportion of methylprednisolone recipients than untreated participants developed OHSS (10.0% vs. 43.9%). Treatment recipients had more oocytes retrieved and more embryos fertilized than did untreated participants. Methylprednisolone treatment was equally effective in preventing OHSS in all causes of infertility and was effective independent of the number of IVF trials and pregnancy rates.CONCLUSION(S): Treatment with methylprednisolone appears to reduce the risk for OHSS. This treatment thus helps to avoid hospitalization, reduces

Fertil Steril 2002 Sep;78(3):520-8
Efficacy and safety of highly purified menotropin versus recombinant follicle-stimulating hormone in in vitro fertilization/intracytoplasmic sperm injection cycles: a randomized, comparative trial. The European and Israeli Study Group on Highly Purified Menotropin versus Recombinant Follicle-Stimulating Hormone.
Kiel, Augsburg, Germany.
OBJECTIVE: To demonstrate that highly purified human menopausal gonadotropin (HP-hMG) is as efficient and safe as recombinant FSH in females undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles.DESIGN: Multinational, open label, randomized, parallel group, comparative phase III trial.SETTING: In 22 centers across six countries; Belgium (1 center), Germany (6 centers), Israel (6 centers), The Netherlands (2 centers), Switzerland (1 center) and the United Kingdom (6 centers).PATIENT(S): A total of 781 women were enrolled between May 1999 and November 2000.INTERVENTION(S): In the all-patients-treated population, 373 patients received HP-hMG and 354 received recombinant FSH. A long protocol GnRH agonist regimen was used.MAIN OUTCOME MEASURE(S): The primary end point was ongoing pregnancy rate following one IVF/ICSI treatment cycle. Safety was assessed as a secondary end point.RESULT(S): Ongoing pregnancy rates 10 weeks after ovum pickup in the per-protocol population were 25% (n = 85/344) in the HP-hMG group and 22% (n = 71/317) in the recombinant FSH group. The incidence of ovarian hyperstimulation syndrome, miscarriage, adverse events, and injection site reactions (tolerability) were similar in both treatment groups.CONCLUSION(S): We found HP-hMG to be as effective as recombinant FSH in terms of ongoing clinical pregnancy. Both treatments have a similar safety/tolerability profile.

Fertil Steril 2002 Sep;78(3):449-54
Vitrification can be more favorable than slow cooling. Kuleshova LL, Lopata A.
Reproductive Biology Research, Department of Obstetrics and Gynecology, Royal Women's Hospital, University of Melbourne, Australia. kuleshova@ivf.co.jp
OBJECTIVE: Cryopreservation of embryos and oocytes has become an essential service for infertility treatment. The clinical application of this technology should ensure optimal survival of the embryos and oocytes that are stored and subsequently thawed for transfer. The aim of this review is to compare the widely employed slow cooling procedures with vitrification to evaluate and recommend the more effective and safer procedure.DESIGN: The review is mainly based on a comparison of the principles, procedures, and results reported in the literature. A historical description of vitrification and personal experiences with this technology are also included. MAIN OUTCOME MEASURE(S): Reported number of pregnancies established after transfer of embryos that were cryopreserved by vitrification, or transfer of embryos derived from vitrified oocytes.RESULT(S): Both slow cooling and vitrification procedures have resulted in the successful cryopreservation of human embryos and oocytes. Both procedures have resulted in healthy births, although the slow cooling of oocytes gives very low success rates. Vitrification is a promising novel technique in assisted reproductive technology, but comparative success rates are yet to be established.CONCLUSION(S): Vitrification is a simple procedure that requires less time and is likely to become safer and more cost effective than slow cooling.

Gynecol Obstet Invest 2002;53(4):220-3
A Prospective Comparative Study on IVF Outcomes with Either Purified FSH or Human Menopausal Gonadotrophin in Downregulated Normogonadotrophic Women. Ismail AF, Hesham AI, Salah Z, Khaled M, Fouad N, Ashraf N, Hatem S, Hamdi B.
Cairo University, Cairo, Egypt.
OBJECTIVE: In compare the use of purified follicle-stimulating hormone with that of a preparation containing follicle-stimulating hormone and luteinizing hormone in infertile females undergoing IVF. CONCLUSION: Purified FSH yields similar clinical outcome to hMG in terms of oocytes retrieved and clinical pregnancies in a standard IVF regimen.

J Assist Reprod Genet 2002 Jul;19(7):313-8
Comparison between a single dose of goserelin (depot) and multiple daily doses of leuprolide acetate for pituitary suppression in IVF treatment: a clinical endocrinological study of the ovarian response.
Geber S, Sales L, Sampaio MA.
ORIGEN, Centro de Medicina Reprodutiva, Belo Horizonte, Minas Gerais, Brazil. sjgeber@bhnet.com.br PURPOSE: Compare the efficacy and safety of two different GnRHa, used for pituitary suppression in IVF cycles. METHODS: A total of 292 patients using depot goserelin (Group 1) and 167 using daily leuprolide acetate (Group 2) were compared. Days required to achieve pituitary function suppression, duration of ovarian stimulation, total dose of HMG, number of aspirated follicles, number of oocytes retrieved, and presence of functional ovarian cyst were analyzed. RESULTS: The time taken to achieve downregulation was similar. The mean number of ampoules used for superovulation was higher in Group 1; however, this difference was observed only for patients >40 years old that started GnRHa in the follicular phase. There was no difference between the two groups in the duration of superovulation, in the number of follicles aspirated, and the number of oocytes retrieved. In the group of patients with >40 years the incidence of ovarian cysts was higher in Group 2. CONCLUSIONS: Both routes of GnRHa have similar effects for pituitary suppression and ovulation induction in assisted reproductive technology. Therefore the long-acting GnRHa is an excellent option, as only a single subcutaneous dose is necessary, decreasing the risk of the patient to forget its use and, most important, it does not interfere in the patient's quality of life.

J Assist Reprod Genet 2002 Jul;19(7):309-12
Autologous endometrial coculture in patients with a previous history of poor quality embryos. Spandorfer SD, Barmat L, Navarro J, Burmeister L, Veeck L, Clarke R, Liu HC, Rosenwaks Z.
The Center For Reproductive Medicine and Infertility, The New York Hospital, Cornell Medical Center, New York 10021, USA.
PURPOSE: To evaluate the effect of autologous endometrial coculture in patients (less than 36 years old) with a history of a single IVF failed cycle associated with poor quality embryos. METHODS: Design: Controlled clinical study. Setting: University-based in vitro fertilization center. Patients: Twenty-six patients with a history of a single prior failed IVF-ET with poor preembryo quality. Intervention(s): Autologous endometrial coculture. Main outcome measures: Preembryo blastomere numbers and cytoplasmic fragmentation rates were compared between the treatment and previous cycle. Clinical pregnancy rates were analyzed. RESULTS: Twenty-six women with an average age of 32.8 +/- 2.9 years underwent treatment. On Day 3 the overall mean number of blastomeres per preembryo on coculture compared to conventional medium in a previous cycle was 6.1 +/- 1.8 vs. 5.1 +/- 1.3 (P = 0.01; Wilcoxon test). The average percentage of cytoplasmic fragments on coculture compared to the conventional medium in a previous cycle was 14% +/- 10 vs. 22% +/- 13 (P = 0.003; Wilcoxon test). At transfer the mean number of blastomeres per preembryo on coculture was 7.4 +/- 1.8 compared to 6.7 +/- 1.5 on conventional medium in a previous cycle (P = 0.02; Wilcoxon test). The clinical pregnancy rate (positive fetal cardiac activity) per patient was 88.5%. The delivery rate was 73.1% (19/26). CONCLUSIONS: There was an improvement in the preembryo quality for preembryos on autologous endometrial coculture compared to noncocultured preembryos from the same patient in a previous cycle. An excellent delivery rate was subsequently found.

Hum Reprod 2002 Aug;17(8):2027-34
Obstetrical and neonatal outcome after controlled ovarian stimulation for IVF using the GnRH antagonist ganirelix.
Boerrigter PJ, De Bie JJ, Mannaerts BM, Van Leeuwen BP, Passier-Timmermans DP.
NV Organon, Clinical Development Department, P.O.Box 20, 5340 BH, Oss, The Netherlands. BACKGROUND: To establish long-term safety, follow-up data on pregnancy, birth and neonatal outcome were collected during clinical development trials with ganirelix (Orgalutran) in women undergoing controlled ovarian stimulation for conventional IVF or ICSI. METHODS: Results of an analysis of the pooled data of all follow-up data of the phase 2 and 3 programme for the development of ganirelix are presented. Obstetrical data on 340 ongoing pregnancies ( vertical line16 gestational weeks) after ganirelix treatment and 134 pregnancies after GnRH agonist treatment in a long protocol are shown. Furthermore, the neonatal outcome of 432 children [258 (75.9%) singletons, 72 (21.2%) twins and 10 (2.9%) triplets] born in the ganirelix group is presented and compared with 184 children [91 (67.9%) singletons, 36 (26.9%) twins and seven (5.2%) triplets] in the agonist group. CONCLUSIONS: Reviewing the presented data and the literature on obstetric and neonatal outcome after conventional IVF or ICSI, we conclude that a controlled ovarian stimulation protocol including the novel GnRH antagonist ganirelix has been shown to be safe for pregnant women and their newborn babies.

Hum Reprod 2002 Aug;17(8):2022-6
Use of cetrorelix in combination with clomiphene citrate and gonadotrophins: a suitable approach to 'friendly IVF'?
Engel JB, Ludwig M, Felberbaum R, Albano C, Devroey P, Diedrich K.
Division of Reproductive Medicine and Gynecologic Endocrinology, Department of Gynecology and Obstetrics, University Clinic, Ratzeburger Allee 160, 23538 Lubeck, Germany.
BACKGROUND: With the recently introduced GnRH antagonists, soft stimulation protocols on the basis of clomiphene pretreatment should be possible as the pituitary remains fully sensitive at the beginning of the cycle. METHODS: A prospective trial was carried out on 107 patients undergoing IVF treatment using the multiple dose GnRH antagonist protocol (cetrorelix), clomiphene citrate, and either HMG (n = 54) or recombinant FSH (rFSH) (n = 53). Different stimulation protocols were used to find the most appropriate one for clinical application. RESULTS: Both treatment groups, HMG and rFSH, yielded comparable results concerning gonadotrophin dose, stimulation days and pregnancy rate. A mean number of 6.34 +/- 4.4 metaphase II oocytes was retrieved and a mean number of 2.45 +/- 0.65 embryos was transferred. However, the overall rate of premature LH surges was 21.5% (defined as measurement of LH >10 IU/l and progesterone >1 ng/ml) which is unacceptable for clinical practice. CONCLUSIONS: Increasing the daily cetrorelix dose from 0.25 to 0.5 mg might decrease the number of premature LH surges. Soft stimulation protocols with clomiphene should be used cautiously.

Fertil Steril 2002 Aug;78(2):245-51
Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer. Chien LW, Au HK, Chen PL, Xiao J, Tzeng CR.
Department of Obstetrics and Gynecology, Taipei Medical University and Hospital, Taipei, Taiwan. OBJECTIVE: To investigate the correlation of blood flow detected by color Doppler sonography in the endometrial-subendometrial unit with pregnancy outcome of IVF-ET treatments. DESIGN: Prospective clinical study. SETTING: University setting. PATIENT(S): Six hundred twenty-three patients selected prospectively on the day of ET. INTERVENTION(S): Transvaginal ultrasound examination was performed before ET. MAIN OUTCOME MEASURE(S): Association between pregnancy outcome and distribution of endometrial-subendometrial blood flow (primary outcome measure) and between pregnancy rate and endometrial measurements as well as uterine arterial blood flow (secondary outcome measures). RESULT(S): The overall pregnancy rate was 28.4% (177/623) per ET. The pregnancy and implantation rates of patients with the presence of both endometrial and subendometrial flow were 47.8% (64/134) and 24.2% (94/388); for patients with subendometrial flow only, 29.7% (102/343) and 15.8% (153/967); and for patients with no detectable endometrial-subendometrial flow, 7.5% (11/146) and 3.5% (13/376), respectively. The presence of both endometrial and subendometrial blood flow is indicative of good endometrial receptivity, whereas the absence of both represents a poor uterine environment. Nondetectable endometrial-subendometrial flow was associated with women who were older, had a thinner endometrium, and had higher uterine arterial resistance compared with those women who had detectable flow. CONCLUSION(S): Endometrial-subendometrial blood flow distribution pattern assessed by transvaginal color Doppler before ET is correlated with the implantation and pregnancy rate of IVF treatment.

Fertil Steril 2002 Aug;78(2):237-44
Endometrial hormone receptors and proliferation index in the periovulatory phase of stimulated embryo transfer cycles in comparison with natural cycles and relation to clinical pregnancy outcome. Bourgain C, Ubaldi F, Tavaniotou A, Smitz J, Van Steirteghem AC, Devroey P.
Department of Pathology, European Hospital, Rome, Italy. claire.bourgain@az.vub.ac.be OBJECTIVE: To investigate the endometrial steroid receptors and proliferation index in GnRH analogue/hMG-stimulated cycles in comparison with natural cycles and their relation to clinical pregnancy outcome. DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENT(S): Twenty-seven stimulated patients with GnRH agonist and hMG. Twenty normo-ovulatory patients were the natural cycle controls. INTERVENTION(S): Endometrial aspiration biopsies: in stimulated cycles on the day of oocyte retrieval within the ET cycle (Day OPU) (n = 20) or 2 days later (Day OPU + 2) (n = 7); in natural cycles on the natural day of ovulation (Day NO) (n = 10) or on the day of ovulation + 2 (Day NO + 2) (n = 10). MAIN OUTCOME MEASURE(S): Comparison of endometrial maturation, estrogen (ER) and P receptor (PR), and proliferation index by immunohistochemistry in natural and stimulated cycles, correlation with pregnancy outcome in stimulated cycles. RESULT(S): Stimulated cycles Day OPU showed significantly advanced endometrial maturation compared to natural cycles Day NO; stromal ER and glandular and stromal PR staining was lower in stimulated than in natural cycles, but higher on Day OPU than on Day NO + 2; proliferation index was lower in all stimulated cycles. Steroid receptors and proliferation index in stimulated cycles were unrelated to clinical pregnancy occurrence. CONCLUSION(S): Compared to natural cycles, ovarian stimulation induced an imbalance in endometrial ER and PR and led to a profound antimitotic effect in the peri-ovulatory phase. These parameters were, however, not predictive of clinical pregnancy in cycles with ET.

Hum Reprod 2002 Jul;17(7):1901-5
Serum HCG 12 days after embryo transfer in predicting pregnancy outcome. Poikkeus P, Hiilesmaa V, Tiitinen A.
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital and Department of Obstetrics and Gynaecology, South Karelia Central Hospital, Finland. BACKGROUND: Assisted reproduction treatment (ART) entails a risk of ectopic pregnancy and early pregnancy loss. Serum HCG has been found to be predictive of pregnancy outcome. Our aim was to assess the clinical value of a single early HCG assay in ART pregnancies taking into account the aetiology and treatment of infertility. METHODS: During 1994-1999, we studied 774 embryo transfer cycles resulting in pregnancy defined as a serum HCG concentration of vertical line5 IU/l on day 12 following embryo transfer. The treatment included IVF in 518, ICSI in 119, and frozen embryo transfer in 137 cycles. Serum HCG concentrations were measured by fluoroimmunometric assay. Pregnancies were classified as viable (live fetus at vertical line22 weeks gestation) or non-viable (biochemical pregnancy, miscarriage, ectopic pregnancy and molar pregnancy). Data on the outcomes were retrospectively retrieved from the records. CONCLUSIONS: A single HCG reading on day 12 after embryo transfer helps to plan the subsequent follow-up. Male factor infertility and ICSI are associated with relatively low HCG values in viable pregnancies.

Hum Reprod 2002 Jul;17(7):1755-61
Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study.
Isaksson R, Gissler M, Tiitinen A.
Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki and STAKES, National Research and Development Centre of Welfare and Health, Helsinki, Finland.
BACKGROUND: Infertility itself and also assisted reproductive treatment increase the incidence of some obstetric complications. Women with unexplained infertility are reported to be at an increased risk of intrauterine growth restriction during pregnancy, but not for other perinatal complications. METHODS: A matched case-control study was performed on care during pregnancy and delivery, obstetric complications and infant perinatal outcomes of 107 women with unexplained infertility, with 118 clinical pregnancies after IVF or ICSI treatment. These resulted in 90 deliveries; of these, 69 were singleton, 20 twin and one triplet. Two control groups were chosen from the Finnish Medical Birth Register, one group for spontaneous pregnancies (including 445 women and 545 children), matched according to maternal age, parity, year of birth, mother's residence and number of children at birth, and the other group for all pregnancies after IVF, ICSI or frozen embryo transfer treatment (FET) during the study period (including 2377 women and 2853 children). CONCLUSIONS: The overall obstetric outcome among couples with unexplained infertility treated with IVF was good, with similar outcome compared with spontaneous pregnancies and IVF pregnancies generally.

Eur J Obstet Gynecol Reprod Biol 2002 Jul 10;103(2):146-9
Increasing the gonadotrophin dose in the course of an in vitro fertilization cycle does not rectify an initial poor response.
Khalaf Y, El-Toukhy T, Taylor A, Braude P.
Assisted Conception Unit, 4th Floor Thomas Guy House, Guy's Hospital, St. Thomas' Street, SE1 9RT,., London, UK
OBJECTIVE: To evaluate the value of increasing the gonadotrophin dose after 5 days of controlled ovarian stimulation in IVF patients who show an initial poor response to stimulation. SUBJECTS AND METHODS: We identified all IVF cycles between January 1992 and March 1996 in which ovarian response after 5 days of controlled ovarian hyperstimulation (COH) with 225-300IU per day of human menopausal gonadotrophins (hMG; Metrodin or Pergonal) was monitored by measurement of serum estradiol concentrations (n=596 patients). According to estradiol concentration, the daily dose of hMG was doubled or increased to 450IU in 193 patients (group A) or maintained the same in 403 patients (group B). Further cycle monitoring was achieved using serial ultrasound and serum estradiol measurements. RESULTS: The two groups were age-matched. Group A patients experienced a higher cancellation rate despite having a higher mean number of hMG ampoules (59.5 versus 36.2) and a longer duration of stimulation (12.2 versus 10.8 days). They achieved lower levels of serum estradiol on days 9 and 10 of stimulation, produced a lower mean number of oocytes per retrieval (5.8 versus 8.9) and had a lower clinical pregnancy rate per cycle (8.3 versus 23.4%) compared to group B. All differences were statistically significant. CONCLUSION: The poor outcome of cycles with initial low response to COH appears not to be averted by doubling or increasing the hMG dose after 5 days of stimulation.

Eur J Obstet Gynecol Reprod Biol 2002 Jul 10;103(2):140-5
Clinical evaluation of three different gonadotrophin-releasing hormone analogues in an IVF programme: a prospective study.
El-Nemr A, Bhide M, Khalifa Y, Al-Mizyen E, Gillott C, Lower AM, Al-Shawaf T, Grudzinskas JG.
Fertility Centre, Royal Hospitals NHS Trust, St Bartholomew's Hospital, West Smithfield, EC1A, London, UK.
The efficacy and safety of short acting buserelin and nafarelin intranasal spray were compared to long acting leuprorelin depot intramuscular or subcutaneous injection in this prospective study of 157 women undergoing controlled ovarian hyperstimulation (COH) for in-vitro fertilisation (IVF). Apart from a statistically significantly greater incidence of allergic nasal reactions in the nafarelin group (P=0.001), all other side-effects were not shown to be statistically significantly different between the three groups. We conclude that a single dose of leuprorelin depot can be considered to be as an equally effective alternative to multiple doses of buserelin or nafarelin for pituitary desensitisation in women undergoing COH for IVF.

Fertil Steril 2002 Jun;77(6):1209-13
Importance of the biopsy date in autologous endometrial cocultures for patients with multiple implantation failures.
Spandorfer SD, Barmat LI, Navarro J, Liu HC, Veeck L, Rosenwaks Z.
The Center for Reproductive Medicine and Infertility, Department of Obstetrics and Gynecology, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, New York 10021, USA. sdspando@mail.med.cornell.edu
OBJECTIVE: To analyze the effectiveness of autologous endometrial coculture by the cycle day of the endometrial biopsy. DESIGN: Retrospective study. SETTING: University-based IVF center. PATIENT(S): Two hundred eight patients with multiple IVF failures. INTERVENTION(S): Embryos were split and randomly allocated to growth on autologous endometrial coculture or conventional media. MAIN OUTCOME MEASURE(S): Embryo quality and pregnancy outcome. RESULT(S): The overall clinical pregnancy rate was 41.8%. Embryos grown on autologous endometrial coculture were of higher quality (more blastomeres and less fragmentation) than embryos grown with conventional media. Early luteal biopsies (<5 days after LH surge) for autologous endometrial coculture did not demonstrate an improvement in embryo quality as compared to the significant improvement demonstrated with later luteal endometrial biopsies (> or =5 days after LH surge). The date of the biopsy was predictive of pregnancy outcome when using autologous endometrial coculture (44.7% [> or =5 days after LH surge] vs. 18.8% [<5 days after LH surge], P=.012). CONCLUSION(S): We have demonstrated an improvement in embryo quality when using autologous endometrial coculture. The improvement in embryo quality and higher pregnancy rates were limited to biopsies > or =5 days after the LH surge. This suggests that mid/late luteal phase endometrium contains factors that enhanced embryo growth and subsequent implantation.

Fertil Steril 2002 Jun;77(6):1202-8
Comparison of the efficacy and safety of a highly purified human follicle-stimulating hormone (Bravelle) and recombinant follitropin-beta for in vitro fertilization: a prospective, randomized study.
Dickey RP, Thornton M, Nichols J, Marshall DC, Fein SH, Nardi RV; Bravelle IVF Study Group.
The Fertility Institute of New Orleans, New Orleans, Louisiana, USA. OBJECTIVE: To compare the efficacy and safety of Bravelle s.c., Bravelle i.m., and Follistim s.c. in patients undergoing controlled ovarian hyperstimulation for IVF-ET. DESIGN: Open-label, randomized, parallel group, multicenter study. SETTING: Eleven academic and private fertility clinics with experience in IVF-ET. PATIENT(S): Infertile premenopausal women with regular ovulatory menstrual cycles undergoing IVF-ET. INTERVENTION(S): Down-regulation with leuprolide acetate followed by up to 12 days of Bravelle s.c. (n = 60), Bravelle i.m. (n = 59), or Follistim s.c. (n = 58); hCG administration, oocyte retrieval, and ET. MAIN OUTCOME MEASURE(S): Mean number of oocytes retrieved; patients with ET, chemical, clinical and continuing pregnancies; mean peak serum E2 levels; adverse events and injection site pain scores. RESULT(S): There were no significant differences among treatment groups in mean number of oocytes retrieved, peak serum E2 levels, patients with ET, continuing pregnancies, or live births. There were no significant differences among the treatment groups in the number, nature, or intensity of adverse events. Patients treated with Bravelle s.c. or Bravelle i.m. experienced significantly less injection site pain than patients treated with Follistim s.c. CONCLUSION(S): Bravelle s.c. and Bravelle i.m. are comparable in efficacy and safety to Follistim s.c. in patients undergoing controlled ovarian hyperstimulation for IVF-ET.

Hum Reprod 2002 Jun;17(6):1519-24
Young age does not protect against the adverse effects of reduced ovarian reserve-an eight year study.
El-Toukhy T, Khalaf Y, Hart R, Taylor A, Braude P.
Assisted Conception Unit, 4th Floor, Thomas Guy House, Guy's and St Thomas' Hospital NHS Trust, St Thomas' Street, London SE1 9RT, UK.
BACKGROUND: Ovarian reserve significantly influences IVF outcome. Low response to ovarian stimulation due to reduction of ovarian reserve is occasionally encountered in young women. The aim of this study was to evaluate the outcome of IVF treatment in young patients with reduced ovarian reserve. METHODS AND RESULTS: Between January 1993-2001, 762 consecutive patients satisfied the definition of reduced ovarian reserve (raised early follicular phase FSH or gonadotrophin stimulation cycles where three or fewer oocytes were retrieved after routine FSH stimulation) and were included in the study. They were classified into three age groups: young (38 years). The three age groups were similar with respect to basal (day 3) serum FSH and estradiol concentrations, cause of infertility and number of previous treatment cycles. Implantation (13, 9.6 and 9.8%), clinical pregnancy (11.8, 10.2 and 10%) and live birth (7.4, 7.3 and 6.8%) rates were not significantly different in the three age groups respectively (P > 0.05). CONCLUSION: This study shows that younger patients with reduced ovarian reserve have a poor outcome of IVF treatment similar to their older counterparts. Such information may be helpful in counselling these patients who otherwise might anticipate an outcome related to their chronological age.

Hum Reprod 2002 Jun;17(6):1507-12
A prospective randomized study: day 2 versus day 5 embryo transfer. Van Der Auwera I, Debrock S, Spiessens C, Afschrift H, Bakelants E, Meuleman C, Meeuwis L, D'Hooghe TM.
Leuven University Fertility Center, University Hospital Gasthuisberg, Catholic University Leuven, Herestraat 49, B-3000 Leuven, Belgium.
BACKGROUND: This randomized controlled study was performed in an unselected IVF/ICSI population to test the hypothesis that blastocyst transfers result in higher clinical pregnancy rates (CPR) per oocyte retrieval when compared with day 2 transfers. METHODS: Blind randomization for transfer on day 2 (group 1) or day 5/6 (group 2) was performed before stimulation. Oocytes and embryos were cultured in sequential media in 5.5% CO(2), 5% O(2), 89.5% N(2) and 90% humidity. A maximum of two embryos was transferred. RESULTS: The two groups were similar for age, IVF indication, number of treatment cycles, rate of ICSI/IVF, number of fertilized oocytes and number of embryos transferred. The CPR/oocyte retrieval was comparable in group 1 (32%) and in group 2 (44%), while the CPR/embryo transfer was significantly higher (P < 0.01) in group 2 (60%) than in group 1 (35%). Similarly, the implantation rate per embryo transferred was significantly higher (P < 0.03) in group 2 (46%) than in group 1 (29%). The cryo-augmented delivery rate/oocyte retrieval was comparable in group 2 (36.3%) and in group 1 (28.6%). CONCLUSION: This randomized study in an unselected population showed a significantly higher CPR/embryo transfer and a tendency toward a higher CPR/oocyte retrieval in patients receiving blastocysts when compared with day 2 transfers.

Eur J Obstet Gynecol Reprod Biol 2002 Jun 10;103(1):48-52
Luteal phase support using either Crinone((R)) 8% or Utrogest((R)): results of a prospective, randomized study.
Ludwig M, Schwartz P, Babahan B, Katalinic A, Weiss JM, Felberbaum R, Al-Hasani S, Diedrich K.
Department of Gynecology and Obstetrics, Medical University of Lubeck, Ratzeburger Allee 160, 23538, Lubeck, Germany
The Crinone((R)) 8% preparation makes it possible to administer natural progesterone (90mg) vaginally once daily for luteal phase support (LPS). Until now, no prospective, randomized studies have directly compared this new preparation with widely used Utrogest((R)) capsules, which were originally designed for oral administration but are used routinely as a vaginal preparation. A prospective, randomized study investigated 126 patients undergoing cycles of in vitro fertilization (IVF) and IVF/intracytoplasmic sperm injection (ICSI). Patients received either Crinone((R)) 8% (n=73) vaginally once daily or two Utrogest((R)) capsules (n=53) vaginally three times daily (600mg). Clinical pregnancy rates were comparable (28.8 versus 18.9%), as were clinical abortion rates until 12 weeks of gestation (14.3 versus 10.0%) and clinical ongoing pregnancy rates (24.7 versus 17.0%) in the Crinone((R)) 8% and Utrogest((R)) groups, respectively. Forty-seven non-pregnant patients were randomly selected to answer questions regarding comfort during LPS. Crinone((R)) 8% had a clear advantage over Utrogest((R)) as it resulted in less vaginal discharge (P<0.01) and fewer application difficulties (P<0.05). Twenty patients familiar with the alternative preparation from a previous cycle also noted that Crinone((R)) 8% was easier to apply (P<0.01) and less time consuming (P<0.05) to use than Utrogest((R)).

J Assist Reprod Genet 2002 Apr;19(4):164-8
Ascorbic acid supplement during luteal phase in IVF. Griesinger G, Franke K, Kinast C, Kutzelnigg A, Riedinger S, Kulin S, Kaali SG, Feichtinger W.
Department of Obstetrics and Gynecology, University of Vienna, Waehringer Guertel, Austria.
PURPOSE: To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospective, randomized, placebo-controlled, group comparative, double-blind study. METHODS: Voluntary daily oral intake of either ascorbic acid (1, 5, or 10 g/day) or Placebo for 14 days after follicle aspiration for IVF-ET procedure. Data was obtained on 620 cases of women, age <40 years, undergoing first IVF-embryo transfer cycles in two private outpatient infertility clinics. All women were stimulated by the same protocol. The mean age was 31.73 (+/- 4.4 SD) years. RESULTS: No differences in clinical pregnancy rate and implantation rate were noted in statistical logistic regression analysis between the four intake groups. CONCLUSIONS: There was no clinical evidence of any beneficial effect, as defined by main outcome measures, of ascorbic acid on IVF-ET. Our data suggest there is no obvious value of high dosed intake of vitamin C during luteal phase in infertility treatment.

Clin Exp Obstet Gynecol 2002;29(1):42-4
Prognosis following in vitro fertilization-embryo transfer (IVF-ET) in patients with elevated day 2 or 3 serum follicle stimulating hormone (FSH) is better in younger vs older patients.
Check JH, Nazari P, Check ML, Choe JK, Liss JR.
The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden, Cooper Hospital/University Medical Center, Department of Obstetrics and Gynecology, USA. PURPOSE: To determine if younger women with increased day 2 or 3 serum follicle stimulating hormone (FSH) levels have a better prognosis than older women with similar FSH elevations. METHODS: Retrospective comparison of in vitro fertilization (IVF) outcome from cycles from 1/1/97 to 9/30/99 according to serum FSH < or = 12 vs > 12 and age < or = 38 or > 38. Only cycles where follicular phase leuprolide acetate was used were included. RESULTS: Age group < or = 38 - clinical pregnancy rate (PR)/transfer was 32% with lower FSH vs 28.6% with higher FSH. The respective PRs for the older group were 30.3% and 5.5%. CONCLUSIONS: Oocyte quality as evidenced by PRs following IVF-ET seems to be better in younger vs older patients despite increased basal serum FSH levels.

J Reprod Med 2002 Apr;47(4):253-8
GnRH antagonist in older IVF patients. Retrieval rates and clinical outcome. Chang PL, Zeitoun KM, Chan LK, Thornton MH 2nd, Sauer MV.
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York, USA. pchang@chpnet.org OBJECTIVE: To determine if the use of a midcycle GnRH antagonist provides better clinical outcomes and lower cancellation rates in in vitro fertilization (IVF). STUDY DESIGN: We examined all patients older than 40 years undergoing IVF-embryo transfer cycles between January 1999 and December 2000. Prior to June 2000, controlled ovarian stimulation in women > or = 40 years was performed with follicle stimulating hormone (FSH)/human menopausal gonadotropin (hMG) only and no GnRH agonist or antagonist (group I). After June 2000, following the release of Ganirelix in the U.S., all women > or = 40 years were stimulated with FSH/hMG + Ganirelix (group II). Outcomes of IVF cycles prior to Ganirelix were compared to results after its introduction. RESULTS: Cancellation rates were significantly lower in group II (16%) as compared to group I (67%) (P < .05). In patients with oocytes retrieved, group II had a significantly higher number of recovered oocytes (7.7 +/- 0.8 vs. 5.3 +/- 0.7, P < .05). However, the number of embryos transferred, cumulative embryo scores, implantation rates and ongoing pregnancy rates did not differ significantly between groups. CONCLUSION: Although our results are preliminary, the addition of GnRH antagonist avoids ovarian suppression at the start of controlled ovarian hyperstimulation and prevents the premature LH surge at midcycle. Thus, more patients attempting IVF undergo oocyte retrieval, although clinical outcomes may not necessarily be improved.

Fertil Steril 2002 May;77(5):1049-52
The learning curve of selective salpingography and tubal catheterization. Papaioannou S, Afnan M, Girling AJ, Ola B, Hammadieh N, Coomarasamy A, Sharif K.
Birmingham Women's Hospital, Birmingham, United Kingdom Assisted Conception Unit, Birmingham, United Kingdom
OBJECTIVE: To determine the effect of increasing experience in fluoroscopically guided selective salpingography and tubal catheterization on radiation doses and screening times, thus establishing a learning curve for the procedure.DESIGN: Retrospective case note analysis.SETTING: IVF center of an academic teaching hospital.PATIENTS: Three hundred sixty-six patients with infertility seen over 3.5 years.INTERVENTION(S): Fluoroscopically guided selective salpingography and tubal catheterization.MAIN OUTCOME MEASURE(S): Reductions in radiation doses and screening times for different categories of selective salpingography and tubal catheterization, expressed as percentage reductions during the study period and reductions per 10 procedures.RESULT(S): During the study period, The median dose of radiation decreased by 62.6%-71.9%, and the median screening time declined by 61.5%-78.5%. Reductions per 10 procedures were 2.5%-4.2% and 2.7%-5%, respectively.CONCLUSION(S): Significant reductions in radiation doses and screening times start early in a clinical team's practice of selective salpingography and tubal catheterization and continue even as trainees are added to the pool of operators.

1: Fertil Steril 2002 Aug;78(2):245-51
Assessment of uterine receptivity by the endometrial-subendometrial blood flow distribution pattern in women undergoing in vitro fertilization-embryo transfer.
Chien LW, Au HK, Chen PL, Xiao J, Tzeng CR.
Department of Obstetrics and Gynecology, Taipei Medical University and Hospital, Taipei, Taiwan.
OBJECTIVE: To investigate the correlation of blood flow detected by color Doppler sonography in the endometrial-subendometrial unit with pregnancy outcome of IVF-ET treatments. DESIGN: Prospective clinical study. SETTING: University setting. PATIENT(S): Six hundred twenty-three patients selected prospectively on the day of ET. INTERVENTION(S): Transvaginal ultrasound examination was performed before ET. MAIN OUTCOME MEASURE(S): Association between pregnancy outcome and distribution of endometrial-subendometrial blood flow (primary outcome measure) and between pregnancy rate and endometrial measurements as well as uterine arterial blood flow (secondary outcome measures). RESULT(S): The overall pregnancy rate was 28.4% (177/623) per ET. The pregnancy and implantation rates of patients with the presence of both endometrial and subendometrial flow were 47.8% (64/134) and 24.2% (94/388); for patients with subendometrial flow only, 29.7% (102/343) and 15.8% (153/967); and for patients with no detectable endometrial-subendometrial flow, 7.5% (11/146) and 3.5% (13/376), respectively. The presence of both endometrial and subendometrial blood flow is indicative of good endometrial receptivity, whereas the absence of both represents a poor uterine environment. Nondetectable endometrial-subendometrial flow was associated with women who were older, had a thinner endometrium, and had higher uterine arterial resistance compared with those women who had detectable flow. CONCLUSION(S): Endometrial-subendometrial blood flow distribution pattern assessed by transvaginal color Doppler before ET is correlated with the implantation and pregnancy rate of IVF treatment.