Days Of Ovarian Stimulation Research Articles

Corifollitropin alfa in a long GnRH agonist protocol: proof of concept trial

Fifty healthy women, aged 18-39 years with no known risk of ovarian hyperstimulation were treated with 100 or 150 μg corifollitropin alfa (dependent on body weight) in a long GnRH agonist protocol. At these doses, corifollitropin alfa initiated and supported growth of a large cohort of follicles during the first week of ovarian stimulation.

Early hCG addition to rFSH for ovarian stimulation in IVF provides better results and the cDNA copies of the hCG receptor may be an indicator of successful stimulation

A simple, safe and cost-effective treatment protocol in ovarian stimulation is of great importance in IVF practice, especially in the case of previous unsuccessful attempts. hCG has been used as a substitute of LH because of the degree of homology between the two hormones. The main aim of this prospective randomized study was to determine, for the first time, whether low dose hCG added to rFSH for ovarian stimulation could produce better results compared to the addition of rLH in women entering IVF-ET, especially in those women that had previous IVF failures. An additional aim was to find an indicator that would allow us to follow-up ovarian stimulation and, possibly, modify it in order to achieve a better IVF outcome; and that indicator may be the cDNA copies of the LH/hCG receptor. Group A patients (n = 58) were administered hCG and Group B rLH (n = 56) in addition to rFSH in the first days of ovarian stimulation. The number of follicles and oocytes and, most importantly, implantation and pregnancy rates were shown to be statistically significantly higher in the hCG group. This study has also determined, for the first time to our best knowledge, m-RNA for LH/hCG receptors in the lymphocytes of peripheral blood 40 h before ovum pick-up. cDNA levels of the hCG receptor after ovarian stimulation were significantly higher among women receiving hCG compared to those receiving LH. In addition, higher levels were encountered among women with pregnancy compared to those without, although this was not statistically significant due to the small number of pregnancies. It seems that hCG permits a highly effective and more stable occupancy of rLH/hCG receptors and gives more follicles and more oocytes. The determination of cDNA copies could be, in the future, a marker during ovulation induction protocols and of course a predictor for the outcome of ART in the special subgroup of patients with previous failures.

Fertility Preservation for Breast Cancer Patients

Breast cancer is the most common neoplasm in women and accounts for 26% (182,460) of all new cancer cases among women. With the use of screening mammography and advancement in other diagnostic modalities, many cases of breast cancer now can be diagnosed and treated at early stages of the disease. Unfortunately, adjuvant chemotherapy regimens commonly used in the treatment of breast cancer may cause premature ovarian failure due to their cytotoxic effects on the germ cells in the ovary. Therefore preservation of fertility in breast cancer survivors at reproductive age has become an important quality of life issue. Fertility preservation is a recently emerged field of reproductive medicine that may help protect the reproductive capability of the cancer survivors and allow them to have children in the future. Embryo freezing is the most established fertility preservation strategy. But conventional ovarian stimulation protocols are contraindicated in breast cancer patients because of the rise of estrogen and its metabolites to supraphysiological levels. Recently developed ovarian stimulation protocols with aromatase inhibitor letrozole and tamoxifen appear to provide a safe stimulation with endogenous estrogen levels comparable with those achieved in the natural cycle. Oocyte freezing can be considered in single women and in those who do not wish donor sperm. Ovarian tissue freezing could also be an option in breast cancer patients who do not wish or have a time for an in vitro fertilization cycle, which requires 10 to 14 days of ovarian stimulation.

GnRH agonist versus recombinant HCG in an oocyte donation programme: a randomized, prospective, controlled, assessor-blind study

The use of gonadotrophin-releasing hormone (GnRH) agonists for triggering ovulation remains controversial. The primary objective of this study was to evaluate the incidence of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist versus recombinant human chorionic gonadotrophin (HCG) as methods for triggering ovulation. A second aim was to compare the clinical outcome and embryo quality according to the two procedures. The cycle characteristics of 100 oocyte donors undergoing ovarian stimulation and IVF outcomes of their 100 oocyte recipients were analysed. Donors were prospectively randomized into two groups on the last day of ovarian stimulation: Group I received a single bolus of 0.2 mg of triptorelin and Group II received 250 microg of recombinant HCG. No differences were observed in the number of oocytes retrieved or in the proportion of metaphase II oocytes between the groups. The OHSS rate was higher in donors that received recombinant HCG ( P = 0.003). Moreover, there was no significant difference between IVF parameters and outcome in the two groups. In conclusion, a GnRH agonist effectively triggers the final oocyte maturation in oocyte donors without negatively affecting implantation, pregnancy or miscarriage rates. Moreover, this regime effectively eliminates the risk of OHSS in this group of women.

A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol

BACKGROUNDCorifollitropin alfa, a fusion protein lacking LH activity, has a longer elimination half-life and extended time to peak levels than recombinant FSH (rFSH). A single injection of corifollitropin alfa may replace seven daily gonadotrophin injections during the first week of ovarian stimulation.METHODSIn this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 µg corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH antagonist protocol.RESULTSThe study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): −3.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus–oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P = 0.15).CONCLUSIONCorifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH. The trial was registered under ClinicalTrials.gov identifier NTC00696800.

45,X/46,XX mosaicism in female partners of couples undergoing in vitro fertilization or ICSI: effects on treatment outcomes

OBJECTIVE: There is an increased rate of low-level sex chromosome mosaicism (scm) (45,X/46,XX) in the female partners of couples undergoing intracytoplasmic sperm injection (ICSI). 45,X is responsible for diminished ovarian reserve.We realised a retrospective study to evaluate differences in ovarian reserve and in in vitro fertilization (IVF) +/− ICSI outcomes between patients who had scm diagnosed incidentally and controls women. DESIGN: We included women aged from 21 to 43 years referred for IVF or ICSI in our unit and who benefited from a karyotype. MATERIALS AND METHODS: All chromosomal analysis were performed in our laboratory. 71 women with numerical scm (45,X/46,XX) range from 4% to 28% were included in group I. They were adjusted for age at karyotype with 73 control women (46,XX) (group II). Ovarian stimulations protocols and criteria for oocyte retrieval were the same in both groups. X2 and Student's t-tests were used to compare the results. RESULTS: Indications for karyotypes and aetiologies of infertility did not differ between the groups. The two groups did not differ for: age at recruitment (33.9±4.3 vs 33.2±4.2 years; P = 0.31), body mass index, tobacco, menses and dysmenorrhea. Early-follicular-phase blood assessments for FSH, LH, estradiol or TSH were done in our laboratory and no significant difference was found between the groups. Clinical or biological diminished ovarian reserve was no more associated with scm. 122 ICSI plus 34 IVF treatment cycles and 148 ICSI plus 35 IVF treatment cycles were performed in groups I and II respectively. The number of days of ovarian stimulation and total gonadotrophin doses were not different between the two groups. 24 and 18 cycles were cancelled in groups I and II respectively (P = 0.19). No difference was found for the mean number of oocytes retrieved, metaphase II oocytes and atretic oocytes, but mean number of embryos was higher in the group I (3.6±3.5 vs 2.8±2.4; P = 0.02). Among women recruited only for male factor's infertility, mean number of oocytes retrieved was higher in group I (11.2±6.2 vs 8.8±5.2; p=0.02), also mean number of metaphase II oocytes (9.3±5.5 vs 6.6±4.1; P = 0.002) and mean number of embryos (4.8±4.6 vs 3.1±2.7; P = 0.008). Clinical pregnancy rates per oocyte recovery cycle were 18.5% and 19.7 % respectively (P=ns). Pregnancy outcomes did not differ after IVF treatments between groups. CONCLUSIONS: We confirm that sex chromosme mosaicism under 28% of aneuploidy does not negatively affect the course and outcome of IVF or ICSI.

Different ovarian stimulation protocols for women with diminished ovarian reserve

To review the available treatments for women with significantly diminished ovarian reserve and assess the efficacy of different ovarian stimulation protocols. Literature research performed among studies that have been published in the Pubmed, in the Scopus Search Machine and in Cohrane database of systematic reviews. A lack of clear, uniform definition of the poor responders and a lack of large-scale randomized studies make data interpretation very difficult for precise conclusions. Optimistic data have been presented by the use of high doses of gonadotropins, flare up Gn RH-a protocol (standard or microdose), stop protocols, luteal onset of Gn RH-a and the short protocol. Natural cycle or a modified natural cycle seems to be an appropriate strategy. Low dose hCG in the first days of ovarian stimulation has promising results. Molecular biology tools (mutations, single nucleotide polymorphisms (SNPs)) have been also considered to assist the management of this group of patients. The ideal stimulation for these patients with diminished ovarian reserve remains a great challenge for the clinician, within the limits of our pharmaceutical quiver.

Prediction of pregnancy in IVF cycles on the fourth day of ovarian stimulation

Prediction of IVF outcome on the first days of ovarian stimulation has focused clinical research for many years. The aim of this work is to predict the probability of pregnancy on the fourth day of ovarian stimulation for IVF cycle, using parameters usually determined in this stage--estradiol, antral follicle count--together with parameters determined previously: FSH on the third day of cycle and women age. One hundred and ten patients with primary infertility due to a tubal factor were recruited to participate in a prospective study. FSH was determined on the third day of spontaneous cycle. Antral follicles and estradiol were measured on the fourth day of ovarian stimulation. After oocyte pick-up, quality and quantity of oocytes and embryos and pregnancy rates were assessed. In stepwise multiple logistic regression the variables with better predictiveness over pregnancy are: antral follicles count, estradiol and woman age. The logistic regression analyses demonstrate that the capacity of the model that uses these variables to predict pregnancy is 75%, with a positive predictive value of 69% and a negative predictive value of 80%. On the fourth day of ovarian stimulation of IVF cycles, the variables with highest predictiveness are: antral follicle count, estradiol and women age. When these variables are included in a model of prediction, the capacity to predict pregnancy is 75%.

The psychological impact of mild ovarian stimulation combined with single embryo transfer compared with conventional IVF

The objective of this study was to assess the psychological implications of mild ovarian stimulation combined with single embryo transfer (SET) during a first IVF cycle. We conducted a randomized controlled two-centre trial. Three hundred and ninety-one couples were randomized to undergo either mild ovarian stimulation with GnRH antagonist co-treatment and SET (n=199) or conventional GnRH agonist long protocol ovarian stimulation with double embryo transfer (DET) (n=192). Women completed the Hospital Anxiety and Depression Scale, the Hopkins Symptom Checklist and the Subjective Sleep Quality Scale at baseline, on the first day of ovarian stimulation and following embryo transfer. Affect was assessed daily with the Daily Record Keeping Chart from the first day of ovarian stimulation until the day treatment outcome became known. The conventional IVF group experienced elevated levels of physical and depressive symptoms during pituitary downregulation. At oocyte retrieval, this group experienced more positive affect and less negative affect than the mild IVF group. In the conventional IVF group, cycle cancellation was associated with less positive and more negative affect. During the first IVF treatment cycle, mild ovarian stimulation and SET does not lead to more psychological complaints than conventional IVF.

When Oocyte Donors Are Treated With GnRH Antagonist Cetrorelix, Changes in Time of Supplement With Recombinant LH Does Not Affect the Reproductive Outcome of Recipient Patients

When Oocyte Donors Are Treated With GnRH Antagonist Cetrorelix, Changes in Time of Supplement With Recombinant LH Does Not Affect the Reproductive Outcome of Recipient Patients

Serum CA-125 and inhibin B levels in the prediction of ovarian response to gonadotropin stimulation in in vitro fertilization cycles

There is much controversy about the relationship between serum CA-125 levels during in vitro fertilization (IVF) cycles and ovarian function. To evaluate the prognostic value of serum CA-125 and inhibin B measurements in predicting ovarian response to gonadotropin stimulation, we compared the CA-125 and inhibin B levels of poor and normal responders on the first day of ovarian stimulation, on the day of ovulation induction (OI) and at oocyte pick-up. Sixteen patients with poor ovarian response ( ⩽ 3 oocytes, serum estradiol (E2) ⩽ 900 pg/ml at OI) in IVF/intracytoplasmic sperm injection cycles were matched with normal responders ( ⩾ 6 oocytes, E2 ⩾ 1800 pg/ml) by age, spontaneous cycle day-3 follicle-stimulating hormone level and cause of infertility. Inhibin B concentrations were significantly lower at all three time points in poor responders, but CA-125 levels were not. No statistically significant correlation was found between CA-125 levels and any of the clinical or laboratory parameters examined. Thus, CA-125 measurements during stimulation are not useful in predicting or identifying poor ovarian response to gonadotropin stimulation in IVF cycles. The lack of difference in CA-125 concentrations between poor and normal responders and lack of correlation with E2 or inhibin B levels suggest that ovarian steroidogenesis and other granulosa cell functions do not influence the production of CA-125. Inhibin B, however, seems to predict ovarian response as early as at the start of stimulation.

The phosphodiesterase 3 inhibitor ORG 9935 inhibits oocyte maturation during gonadotropin-stimulated ovarian cycles in rhesus macaques

To determine whether phosphodiesterase (PDE) 3 inhibitors prevent the resumption of meiosis by primate oocytes in vivo, rhesus macaques were stimulated to develop multiple preovulatory follicles by administering human recombinant gonadotropins, and follicles were aspirated 34 h after an ovulatory stimulus (human chorionic gonadotropin [hCG]). Monkeys received no further treatment (controls) or the PDE3 inhibitor ORG 9935 (a) exclusively in the periovulatory interval beginning 6–12 h prior to receiving hCG at 200 mg/kg every 12 h orally (PER200) or a 200 mg/kg oral loading dose followed by 50 mg/kg sc every 6 h (PER50) or (b) throughout the ovarian stimulation protocol with daily increases until a dose of 200 mg/kg bid was administered onward from the eighth day of ovarian stimulation (EXT200). The primary outcome was the number of oocytes that had resumed meiosis (germinal vesicle breakdown [GVBD]) at collection. At initial aspiration, 85% of oocytes recovered from control animals ( n=4) had progressed to GVBD compared with 53% (p<.01), 23% (p<.01), and 13% (p<.01) recovered from animals in the PER200 ( n=2), PER50 ( n=1) and EXT200 ( n=3) groups, respectively. Although spontaneous maturation of oocytes was observed during follow-up culture in the absence of ORG 9935, none of the oocytes in the PER50 or EXT200 underwent normal fertilization in vitro. These results demonstrate that the PDE3 inhibitor ORG 9935 blocks oocyte maturation during gonadotropin-stimulated ovarian cycles in rhesus macaques and suggest that PDE3 inhibitors have potential clinical use as contraceptives in women.

The Phosphodiesterase 3 inhibitor org 9935 inhibits oocyte maturation during gonadotropin-stimulated ovarian cycles in Rhesus macaques

Abstract To determine whether phosphodiesterase (PDE) 3 inhibitors prevent the resumption of meiosis by primate oocytes in vivo, rhesus macaques were stimulated to develop multiple preovulatory follicles by administering human recombinant gonadotropins, and follicles were aspirated 34 h after an ovulatory stimulus (human chorionic gonadotropin [hCG]). Monkeys received no further treatment (controls) or the PDE3 inhibitor ORG 9935 (a) exclusively in the periovulatory interval beginning 6���12 h prior to receiving hCG at 200 mg/kg every 12 h orally (PER200) or a 200 mg/kg oral loading dose followed by 50 mg/kg sc every 6 h (PER50) or (b) throughout the ovarian stimulation protocol with daily increases until a dose of 200 mg/kg bid was administered onward from the eighth day of ovarian stimulation (EXT200). The primary outcome was the number of oocytes that had resumed meiosis (germinal vesicle breakdown [GVBD]) at collection. At initial aspiration, 85% of oocytes recovered from control animals ( n =4) had progressed to GVBD compared with 53% (p n =2), PER50 ( n =1) and EXT200 ( n =3) groups, respectively. Although spontaneous maturation of oocytes was observed during follow-up culture in the absence of ORG 9935, none of the oocytes in the PER50 or EXT200 underwent normal fertilization in vitro. These results demonstrate that the PDE3 inhibitor ORG 9935 blocks oocyte maturation during gonadotropin-stimulated ovarian cycles in rhesus macaques and suggest that PDE3 inhibitors have potential clinical use as contraceptives in women.

Serum leptin concentrations in patients with severe ovarian hyperstimulation syndrome during in vitro fertilization–embryo transfer treatment

To investigate the changes in serum leptin concentration in the conception cycle of severe ovarian hyperstimulation syndrome (OHSS). Prospective longitudinal study of 66 IVF-ET cycles between May 2000 and June 2002. Infertility outpatient clinic at a Japanese medical school. Infertile patients undergoing IVF-ET cycles at the infertility outpatient clinic were divided into three groups consisting of group 1 (conception-cycle patients with severe OHSS, n = 9), and group 2 (conception cycle, non-OHSS, n = 28), and group 3 (nonconception cycle, non-OHSS, n = 29). Blood samples were collected at five different periods. Period I, on the first day of ovarian stimulation with FSH; period II, at hCG administration before oocyte retrieval; period III, 7 days after oocyte retrieval; period IV, 14 days after oocyte retrieval; and period V, 21 days after oocyte retrieval. Serum leptin concentration. The serum leptin concentration was low in the OHSS group compared with that of the non-OHSS groups in all serum samples, with significant levels at periods III (vs. groups 2 and 3; P<.05) and IV (vs. group 3; P<.01). A twofold increase of leptin concentration from period I to period II (P<.05) was observed in all groups. The change pattern in serum leptin concentration might provide a great contribution to the pathophysiology development of OHSS patients during assisted reproductive treatment.

Role of utero–ovarian vascular impedance: predictor of ongoing pregnancy in an IVF–embryo transfer programme

The objective of this study was to evaluate the role of uterine, endometrial and follicular blood flow in prediction of ongoing pregnancy after assisted conception. A prospective observational study was conducted on 53 women undergoing IVF treatment. Transvaginal colour and pulsed Doppler measurements were performed on the day that pituitary suppression was confirmed, on day 10 of ovarian stimulation and on the day prior to human chorionic gonadotrophin injection. On the last day of ovarian stimulation, blood flow in the ascending uterine artery of the women who would conceive was characterized by significantly lower pulsatility index values. Sub-endometrial vascular impedance was comparable in the pregnant and non-pregnant groups. There were no differences in the perifollicular vascularity between pregnant and non-pregnant women. The chance of achieving pregnancy predicted by uterine artery Doppler and perifollicular blood flow in women whose PI values were higher than 3.26 and 1.08 was very low, with a sensitivity of 1.00 and specificity of 0.59 and 0.82 respectively. The data provide evidence for an association between utero–ovarian perfusion and reproductive outcome following IVF treatment. Uterine and ovarian vascular impedance values identify those women whose pregnancy chances are significantly limited. Measures to decrease vascular impedance in such women might enhance pregnancy rates by improving embryo quality and uterine receptivity for implantation.

Serum leptin concentration during in vitro fertilization treatment with controlled ovarian hyperstimulation: Serum leptin concentration decreases in the early luteal phase in pregnancy

Purpose: To investigate the change pattern of leptin during in vitro fertilization and embryo transfer (IVF‐ET) treatment with controlled ovarian hyperstimulation (COH) and at the stages of very early pregnancy.Methods: The serum leptin concentration was investigated in 65 patients treated with assisted reproductive technology (ART) in five different periods (ART‐1: on the first day of ovarian stimulation with follicle‐stimulating hormone; ART‐2: at human chorionic gonadotropin administration before oocyte retrieval; ART‐3: 7 days after oocyte retrieval; ART‐4: 14 days after oocyte retrieval and ART‐5: 21 days after oocyte retrieval).Results: The leptin concentration showed significant lower values in the pregnancy group than the non‐pregnancy group at ART‐3 and ART‐4 (P &lt; 0.05). In the pregnancy group, leptin concentration increased from ART‐1 (13.5 ± 8.2 ng/mL) to ART‐2 (23.0 ± 15.1 ng/mL) (P &lt; 0.001). The values significantly decrease at 7 days after oocyte retrieval, from ART‐2 to ART‐3 (18.1 ± 12.0 ng/mL) (P &lt; 0.01), and then showed no remarkable change until 21 days after oocyte retrieval. In the non‐pregnancy groups, leptin concentration increased from ART‐1 (17.3 ± 11.5 ng/mL) to ART‐2 (25.7 ± 12.1 ng/mL) (P &lt; 0.0001). There was no remarkable change in leptin concentration until 14 days after oocyte retrieval, followed by a significant decrease in leptin concentration at ART‐4 (21.9 ± 11.9 ng/mL) to ART‐5 (18.1 ± 11.8 ng/mL) (P &lt; 0.05).Conclusion: The serum leptin concentration increases during COH in the pregnancy and non‐pregnacy groups. In the pregnancy group, leptin concentration showed a fall of leptin values at early luteal phase. These findings might be useful to elucidate the role of leptin in the IVF‐ET patients. (Reprod Med Biol 2003; 2: 177–182)

Uso de antagonista de GnRH (cetrorelix) em dose única para evitar ovulações prematuras em ciclos de fertilização assistida

OBJETIVO: verificar a eficácia de uma dose única subcutânea de acetato de cetrorelix em evitar a ovulação prematura em ciclos de fertilização assistida. MÉTODOS: estudo prospectivo, randomizado e controlado, pelo qual foram avaliados 20 ciclos de estimulação ovariana em mulheres submetidas a fertilização assistida, 10 das quais utilizaram o esquema tradicional de bloqueio hipofisário com análogos de GnRH em doses diárias (grupo controle) e 10 utilizaram antagonista de GnRH em dose única de 3 mg no 7º dia de estimulação ovariana (grupo cetrorelix). Foram dosados FSH, LH, estradiol e progesterona no soro no primeiro e sétimo dia da estimulação, no dia da injeção de HCG e no dia da captação de oócitos. Os grupos foram comparados entre si quanto a eficácia do bloqueio hipofisário (nível de progesterona no dia da aplicação do HCG) e desempenho nos ciclos de fertilização assistida (ampolas de gonadotrofinas utilizadas, folículos maiores que 18 mm, oócitos captados, taxas de fertilização, implantação e gravidez) utilizando os testes de Mann-Whitney e exato de Fisher. RESULTADOS: não houve diferença significativa entre os grupos controle e cetrorelix, respectivamente, para a mediana da idade (31,5 e 34 anos), índice de massa corpórea (24 e 22), ampolas de gonadotrofinas utilizadas (34 e 32), folículos recrutados (3,5 e 3,0), oócitos captados (11 e 5), embriões obtidos (4 e 3), taxas de fertilização (93,7 e 60%, p = 0,07) e gravidez (50 e 60%, p = 0,7). Em ambos os grupos observou-se bloqueio hipofisário eficaz durante o período de estimulação ovariana. CONCLUSÕES: estes resultados confirmam a eficácia da dose única de 3 mg de acetato de cetrorelix em prevenir ovulações prematuras em pacientes submetidas a fertilização assistida, mostrando tendência a obtenção de menor número de embriões e menores taxas de fertilização no grupo cetrorelix em relação ao grupo controle. As taxas de implantação e gravidez foram semelhantes entre os dois grupos. Estudos prospectivos com maior número de pacientes são necessários para confirmar estes achados.

Advancing age is associated with increased AUC (area under the curve) for E2 (estradiol) production per mature follicle and decreased AUC per FSH stimulation irrespective to the protocol of ovarian stimulation

Objective: To study the effect of age on the pattern of estrogen production per mature ovarian follicle and in response to FSH stimulation during different ovarian stimulation protocols Design: Retrospective. Materials and Methods: Patients undergoing ovarian stimulation in conjunction with intrauterine insemination or for IVF-ET (in vitro fertilization and embryo transfer) have been included from two tertiary referral academic infertility centers in the period from January 2000 and July 2002. Patients were divided into two groups, first group included patients who underwent COH (controlled ovarian hyperstimulation) for IVF-ET (226 patients had 254 cycles). Both standard and microdose flare protocol were applied for COH. The second group included 357 patients who received different ovarian stimulation protocols in conjunction with IUI (intrauterine insemination) in 493 cycles. Clomiphene citrate was used alone in 176 cycles and in conjunction with FSH in 28 cycles, FSH injection alone in 87 cycles, letrozole (an aromatase inhibitor) was used alone in 84 cycles and in conjunction with FSH in 118 cycles). The AUC for E2 production was calculated from available daily E2 levels along the follicular phase starting on the first day of ovarian stimulation until the day of hCG administration (or endogenous LH surge in IUI cycles). AUC for E2 production per FSH unit administered (AUC/FSH) as well as the AUC for E2 produced per mature follicle (AUC/follicle) were calculated. Patients were sub-grouped according to the age in ascending matter. Each patient group was analyzed separately and after subdividing them according to the protocol of ovarian stimulation. Results: Group 1 (IVF) patients had a positive correlation between AUC/follicle and advancing age (P<0.05) and a negative correlation between AUC/FSH and advancing age (P<0.05). This was true when all patients were analyzed together and after subgrouping according to the stimulation protocol (long standard and microdsoe flare up protocol). The same findings were found in the second patient group when all patients were analyzed together and when subdivided into different ovarian stimulation protocol. Pregnancy rates negatively correlated well with advancing age as expected and was also negatively correlating with increasing AUC/follicle and decreasing AUC/FSH. The effect of age on AUC/follicle, AUC/FSH and Pregnancy Rate in IVF-ET cycles Tabled 1 View Large Image Figure ViewerDownload (PPT) Conclusions: High AUC/follicle and low AUC/FSH seem to be features of advancing age irrespective of type of ovarian stimulation. Both parameters also might serve as predictors for poor treatment outcome.

A retrospective analysis of factors influencing oocyte degeneration post-ICSI

Objective: To understand better why some oocytes degenerate after ICSI, we investigated potential correlations between oocyte degeneration rates and: a) patient age; b) day 3 FSH; c) days of ovarian stimulation; d) type of stimulation; e) estradiol (E2) level on day of hCG administration; f) number of oocytes retrieved; g) oocyte maturity at time of cumulus stripping and ICSI; and h) the interval between oocyte retrieval, cumulus stripping, and ICSI. We hypothesized that increased degeneration rates would correlate to poorer prognosis indicators such as, increased patient age, elevated day 3 FSH, and lower E2 levels. Design: A retrospective analysis. Materials and Methods: Data were collected from all ICSI cases during the last six months of 2002 (497 cases, 4933 injected oocytes), analysis was conducted between oocyte degeneration and the previously mentioned variables. Correlations were evaluated non-parametrically using Spearman’s Rho due to the highly non-normal distribution of oocyte degeneration rates. Stepwise multiple regression analysis of ranked data values was used to model the influence of multiple independent variables on oocyte degeneration rates. Results: The percentage of oocyte degeneration after ICSI was significantly correlated to four of the analyzed variables: a younger patient age (Rho = −0.098, P = 0.028); a higher E2 level on day of hCG (Rho = 0.106, P = 0.018); a larger number of oocytes injected (Rho = 0.151, P = 0.0007); a longer period between oocyte retrieval and ICSI (Rho = 0.127, P = 0.0045). The number of injected oocytes was also correlated with each of the other three variables (Rho = −0.242, p < 0.0001 for age, Rho = 0.646, P < 0.0001 for E2 level, and Rho = 0.183, P < 0.0001 for period between retrieval and ICSI). Stepwise multiple regression analysis indicated that oocyte degeneration rates were significantly influenced both by the number of oocytes injected (P = 0.0035), and by the interval between retrieval and ICSI (P = 0.022), but not by age (P = 0.152) or E2 level (P = 0.77). Conclusion: Contrary to our expectations, the strongest correlation observed suggested that cases with more oocytes for injection are more likely to have a higher rate of degeneration. On the other hand, it was not surprising to find that a longer duration in vitro prior to ICSI negatively affected oocyte survival. The negative correlation between age and oocyte degeneration, and the positive correlation between E2 level and oocyte degeneration appear to be indirect results of relatively strong correlations between both age and E2 level, and the number of mature oocytes.

Percutaneous oocyte retrieval from an inguinal ovary

Ectopic locations of the ovary are rare, but should be considered when an ovary is absent on traditional imaging studies. The images presented are of a patient with recurrent pregnancy loss and infertility. Of note, she also had a corrected tetralogy of Fallot and normal karyotype. Hysterosalpingogram revealed a right unicornuate uterus with the presence and patency of only the right fallopian tube. Magnetic resonance imaging showed an absent left kidney and ovary and a left inguinal hernia. The left ovary was discovered on the seventh day of ovarian stimulation for in vitro fertilization when a mass was seen in the inguinal region (Fig. 1) with follicles visualized by transabdominal ultrasound. The risk of ovarian torsion was discussed with the patient who elected to continue the cycle. Oocyte retrieval was performed from the right ovary transvaginally. Then, using a transvaginal ultrasound probe with needle guide (Figs. 2 and 3), the needle was advanced percutaneously through the abdominal wall into the inguinal ovary allowing aspiration of normal-appearing oocytes. The patient did not conceive with the fresh transfer of a single blastocyst but conceived after a thaw transfer of a single embryo and delivered a healthy female at 34 weeks’ gestation. She plans to undergo corrective surgery to repair the inguinal hernia and reposition the ovary into the pelvic cavity.