Clinical outcome of using ganirelix acetate versus a 4-day follicular phase leuprolide acetate protocol in unselected women undergoing in vitro fertilization

OBJECTIVE: To compare the clinical outcome of controlled ovarian hyperstimulation (COH) in unselected patients undergoing IVF using multidose ganirelix acetate versus 4 days of administration of leuprolide acetate. DESIGN: Retrospective cohort study. SETTING: A fertility and IVF center. PATIENT(S): Two hundred forty-seven women who underwent COH-IVF between April 1, 1999, and January 30, 2001. INTERVENTION(S): Pituitary suppression according to a 4-day follicular phase leuprolide acetate protocol (236 women) or a multidose ganirelix acetate regimen (133 women). MAIN OUTCOME MEASURE(S): Amount of gonadotropin used, days of stimulation, cancellation rate, number of oocytes retrieved, implantation rate, and clinical pregnancy rate. RESULT(S): Compared with leuprolide acetate recipients, ganirelix recipients required significantly less gonadotropin and the mean day of hCG administration was 4 days earlier. Among women younger than 35 years of age, the implantation rate (15% vs. 6%) and the clinical pregnancy rate per initiated and transferred cycle (27% vs. 12% and 32% vs. 15%, respectively) were significantly higher in the ganirelix group than the leuprolide acetate group. CONCLUSION(S): Compared with a 4-day leuprolide acetate protocol, COH-IVF using a multidose ganirelix acetate protocol reduces treatment duration and amount of gonadotropin used. In younger women, the latter protocol is associated with significantly better pregnancy and implantation rates.     

Presurgical short term treatment of uterine fibroids with different doses of cetrorelix acetate: a double-blind, placebo-controlled multicenter study

Objective

To assess the efficacy and safety of different dosing schedules of cetrorelix acetate as a short term treatment for 4 weeks prior to surgery in patients with uterine fibroids.

Study design

Randomized, double-blind, placebo-controlled study. Patients were 109 premenopausal women, with at least one uterine fibroid, more than 4 cm in diameter. Groups 1–3 received placebo, 5 and 10 mg of cetrorelix on days 1, 8, 15 and 22, respectively group 4 received 10 mg of cetrorelix on days 1 and 15. MRI scan was performed at screening and on day 29. The main outcome measure was the reduction of uterine volume on day 29 and response, defined as >30% size reduction.

Results

Mean (±S.D.) reduction of uterine volume on day 29 (MRI scan) was 5.1 ± 32.1% with placebo, 15.6 ± 20.2% with 4 × 5 mg, 15.4 ± 34.6% with 4 × 10 mg and 0.6 ± 30.6% with 2 × 10 mg cetrorelix. Significant response versus placebo (p < 0.05) occurred in the 4 × 10 mg group (42.3% versus 11.1%)

Conclusions

Best objective response after 4 weeks of treatment was achieved after therapy with 4 × 10 mg of cetrorelix acetate. Short term presurgical treatment with the LHRH-antagonist cetrorelix is a flexible treatment protocol without any major side effects.     

Ovarian suppression treatment prior to in-vitro fertilization and embryo transfer in Chinese women with stage III or IV endometriosis.

OBJECTIVE: To evaluate the efficacy of a 2-month treatment with a gonadotropin-releasing hormone (GnRH) agonist prior to in-vitro fertilization in Chinese women with moderate or severe endometriosis. METHODS: A study of 162 women surgically diagnosed as having moderate or severe endometriosis. Pituitary down-regulation was achieved with injections of a GnRH agonist prior to the IVF procedures either for 7 to 10 days in the mid-luteal phase (group 1 [standard protocol], 97 cycles in total), or for 2 months (group 2, 55 cycles), or 3 months (group 3, 75 cycles). RESULTS: Women pretreated with a GnRH agonist for 2 or 3 months required significantly higher doses of gonadotropin for ovarian stimulation (P<0.001), and for a longer time, than those treated with the standard long protocol (P<0.05). The number of oocytes and good embryos was lower in group 3 than in groups 1 or 2 (P<0.05). The implantation rate was significantly higher in group 2 than in group 1 (P<0.02). CONCLUSION: A 2-month treatment with a GnRH agonist prior to IVF produced a trend toward an increase in the implantation rate in a group of Chinese women with stages III and IV endometriosis.     

Scanning electron microscopy of human sperms after preparation of semen for in-vitro fertilization

Summary Ultrastructural changes of human sperms after routine preparation for invitro fertilization were examined by scanning electron microscopy. Studies were performed with freshly ejaculated semen of 21 normozoospermic patients. Spermatozoa were analysed at 10000-fold (sperm head with acrosome, postacrosomal border and postnuclear cap) and 2500-fold (midpiece and endpiece of sperm tail) magnification. Compared with untreated specimens, slight membrane damage was found after routine washing and centrifugation procedures in swim-up preparations. However, on the basis of a score system for quantification of morphologic data, no statistically significant differences existed between untreated semen and swim-up preparations. We conclude that, with normozoospermic semen, the rate of ultrastructural damage attributable to sperm-washing procedures is too low to be of clinical consequence.     

Phase II study of cetrorelix,a luteinizing hormone-releasing hormone antagonist in patients with platinum-resistant ovarian cancer

OBJECTIVE: The goal of this work was to study the anticancer activity of cetrorelix, a decapeptide with LHRH receptor antagonist properties in patients with platinum-resistant ovarian cancer. About 80% of primary ovarian cancers and cell lines bear LHRH receptors. Cetrorelix has anticancer activity in in vitro and in vivo ovarian cancer models. METHODS: Eligible patients with ovarian or mullerian carcinoma resistant to platinum chemotherapy received cetrorelix 10 mg subcutaneously every day. Eligibility criteria included age > or = 18, PS < or = 2, measurable disease, chemistries and blood counts in normal range, no estrogen replacement for at least 2 weeks, and no known allergic reactions to extrinsic peptide. In patients volunteering for a biopsy, tissue was taken to perform a LHRH receptor assay. RESULTS: Seventeen patients were treated. Median age was 58 years. Median performance status was 0. Median number of prior chemotherapies was 3. Three patients had partial remissions lasting 9, 16, and 17 weeks. Toxicities effects included grade 4 anaphylactoid reaction (one patient) controlled by cortisol and cimetidine, grade 2 histamine reaction (two patients), grade 2 arthralgia (one patient) 20% cholesterol increase (two patients, who did not require specific treatment), minor hot flushes, headache, and local skin reaction at the injection site. Six of seven samples were LHRH receptor positive for mRNA and/or ligand assay. Two responding patients were LHRH receptor positive. The patient who had no receptor did not respond. CONCLUSION: Cetrorelix has activity against ovarian cancer in this refractory population, and has minimal toxicity, except for potential anaphylactoid reactions. Activity may be mediated through the LHRH receptor.     

Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience

Purpose

To compare the in-vitro fertilization (IVF) outcomes of cancer patients who underwent oocyte retrieval and embryo/oocyte cryopreservation prior to gonadotoxic therapy to those of age and time-matched controls with tubal factor infertility.

Methods

All cancer patients who underwent embryo/oocyte cryopreservation at our institution from 1997 to 2014 were reviewed. Primary outcomes were total dose of gonadotropins used, number of oocytes retrieved, and number of 2pn embryos obtained. Outcomes were compared to age-matched controls with tubal-factor infertility who underwent a fresh embryo transfer within the same relative time period as the IVF cycle of the cancer patient.

Results

Sixty-three cancer patients underwent 65 IVF cycles, and 21 returned for frozen embryo transfer. One hundred twenty-two age-matched controls underwent IVF cycles with fresh transfer, and 23 returned for frozen embryo transfer. No difference was seen between cancer patients and controls with respect to total ampules of gonadotropin used (38.0 vs. 35.6 respectively; p = 0.28), number of oocytes retrieved (12.4 vs. 10.9 respectively; p = 0.36) and number of 2pn embryos obtained (6.6 vs. 7.1 respectively; p = 0.11). Cumulative pregnancy rate per transfer for cancer patients compared to controls was 37 vs. 43 % respectively (p = 0.49) and cumulative live birth rate per transfer was 30 vs. 32 % respectively (p = 0.85). Cancer patients had a higher likelihood of live birth resulting in twins (44 vs. 14 %; p = 0.035).

Conclusions

Most IVF outcomes appear comparable for cancer patients and age-matched controls. Higher twin pregnancy rates in cancer patients may reflect lack of underlying infertility or need for cancer-specific transfer guidelines.     

Acupuncture effects on in-vitro fertilization pregnancy outcomes: A meta-analysis

BackgroundThe effects of acupuncture on in-vitro fertilization outcomes remain controversial. This study aimed to perform a meta-analysis to assess the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization.MethodsA systematic literature search up to January 2021 was performed and 29 studies included 6623 individuals undergoing in-vitro fertilization at the baseline of the study; 3091 of them were using acupuncture as an adjuvant therapy to embryo transfer, 1559 of them were using sham-controls, and 1441 of them were using no adjuvant therapy controls. They reported a comparison between the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls on improving pregnancy outcomes in women undergoing in-vitro fertilization. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated assessing the effectiveness of acupuncture as an adjuvant therapy to embryo transfer compared to sham-controls or no adjuvant therapy controls using the dichotomous method with a random or fixed-effect model.ResultsSignificantly higher outcomes with acupuncture were observed in biochemical pregnancy (OR, 1.98; 95% CI, 1.55–2.53, p < 0.001); clinical pregnancy (OR, 1.70; 95% CI, 1.46–1.98, p < 0.001); ongoing pregnancy (OR, 1.78; 95% CI, 1.41–2.26, p < 0.001); and live birth (OR, 1.58; 95% CI, 1.15–2.18, p = 0.005) compared to no adjuvant therapy controls. However, no significant difference were found between acupuncture and no adjuvant therapy controls in miscarriage (OR, 0.96; 95% CI, 0.48–1.92, p = 0.91).No significant difference was observed with acupuncture in biochemical pregnancy (OR, 1.16; 95% CI, 0.65–2.08, p = 0.62); clinical pregnancy (OR, 1.13; 95% CI, 0.83–1.54, p = 0.43); ongoing pregnancy (OR, 1.04; 95% CI, 0.66–1.62, p = 0.87); live birth (OR, 1.02; 95% CI, 0.73–1.42, p = 0.90), and miscarriage (OR, 1.16; 95% CI, 0.86–1.55, p = 0.34) compared to sham-controls.ConclusionsUsing acupuncture as an adjuvant therapy to embryo transfer may improve the biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth outcomes compared to no adjuvant therapy controls. However, no significant difference was found between acupuncture as an adjuvant therapy to embryo transfer and sham-controls in any of the measured outcomes. This relationship forces us to recommend the use of acupuncture as adjuvant therapy in women undergoing in-vitro fertilization and inquire further studies comparing acupuncture and sham-controls to reach the best procedure.     

Relationship of cytopathology and cervical infection to outcome of in-vitro fertilization and embryo transfer.

OBJECTIVE: To determine whether a relationship exists between in-vitro fertilization and embryo transfer (IVF-ET) outcome and cervical infection or presence of human papillomavirus (HPV). METHOD: Cervical scrapes, digital colposcopies, and cervical biopsies were performed in 1044 Chinese women undergoing IVF for tubal infertility or, in their partners, abnormal semen. The pregnant (n=415) and nonpregnant (n=629) groups differed neither in clinical signs of cervical inflammation nor in rate of HPV detection. RESULTS: There were no associations between IVF-ET outcome and infection rate, degree of cytopathologic abnormality, detection of HPV, or results of digital colposcopy and cervical biopsy. Cytologic results did not correlate with any of the clinical parameters of IVF-ET. CONCLUSIONS: No association was found between IVF-ET outcome and cervical infection, cytopathologic result, HPV detection, or result from the colposcopy or biopsy. Extensive testing and treatment for cervical infection do not appear necessary in IVF-ET candidates.     

Effects of the gonadotropin-releasing hormone antagonist cetrorelix in the early postimplantation period on rat pregnancy

Objective

The effect of cetrorelix given in the early implantation period on rat pregnancy was investigated.

Study design

Forty-nine virgin Sprague-Dawley rats were randomized into six groups. At the 4th or 8th days of sperm plug, groups received 15, 75, 150 μg/kg cetrorelix or saline. Three subjects were randomly selected from each group and sacrificed at 11th gestational day for histomorphometric analysis. The remaining subjects were allowed to complete their pregnancy period. Volumes of total conceptus, labyrinth zone, transitional zone, giant cell zone, and exocoelomic cavity were calculated according to Cavalieri's principle.

Results

Subjects receiving cetrorelix at 15 or 150 μg doses at the 4th day (D4) and those receiving cetrorelix at 150 μg dose at the 8th day (D8) of pregnancy delivered later than the controls. On necropsy examination at the 11th day, mean embryo weights of the cetrorelix 15 D4, 150 D4, 15 D8 and 75 D8 groups were found to be significantly lower than that of the controls (p < 0.05). On histomorphometric evaluation, volumes of the fetuses and the amniotic sacs were decreased by cetrorelix at all doses studied dose dependently. Gross congenital anomalies were observed in the pups of three rats of the cetrorelix 150 D4 and D8 groups.

Conclusion

The results of this study suggest that cetrorelix in the early post-implantation period may lead to serious side effects in the rat.     

The decrease of serum luteinizing hormone level by a gonadotropin-releasing hormone antagonist following the mild IVF stimulation protocol for IVF and its clinical outcome

Purpose While performing the mild ovarian stimulation protocol with a GnRH antagonist, the pregnancy rate was compared between the groups, which were divided by the degree that the luteinizing hormone (LH) level decreased. Materials and methods Patients aged 27 to 42years (36.1 ± 3.79) underwent 308 IVF cycles who opted for IVF via the mild ovarian stimulation protocol began clomiphene citrate on day 3 and recombinant FSH on day 5. A GnRH antagonist was administered when the dominant follicle reached 14mm. Serum LH was measured at the time of GnRH antagonist administration and at the time of hCG injection. The pregnancy rate and implantation rate were compared between 50 cycles in which the LH level dropped less than one-third and the control (LH level within 1/3). Result(s) The pregnancy rate for the group in which the LH level fell less than one third was 18%. Conversely, the pregnancy rate for the control group was 39%. The implantation rate was 18% for the less than one-third group and 26% for the control group. Both the pregnancy rate and the implantation rate for the group in which the LH level fell less than one-third were significantly lower than that of control (p < 0.02). Conslusion(s) When performing the mild ovarian stimulation protocol, serum LH should be followed. If the serum LH level is less than one-third at the time of hCG injection, both the pregnancy rate and implantation rate are significantly lower. Capsule If the serum LH level is less than one-third at the time of hCG injection, both the pregnancy rate and implantation rate are significantly lower following the Mild IVF stimulation protocol.     

Infertile polycystic ovary syndrome patients undergoing in vitro fertilization with the gonadotropin-releasing hormone-antagonist protocol: role of hyperandrogenism

This retrospective cohort study is to assess the effects of hyperandrogenism (HA) in polycystic ovary syndrome (PCOS) patients with gonadotropin-releasing hormone (GnRH)-antagonist protocol during in vitro fertilization (IVF). Total 892 infertile Patients between 20 and 35 years of age with normal body mass index (BMI, 18.50 ?24.99 kg/m²), including those with tubal factor infertility (control, n?=?318), PCOS infertility with HA (HA PCOS, n?=?244), and PCOS infertility without HA (non-HA PCOS, n?=?330), were included. Number of retrieved oocytes was significantly higher and total Gonadotropin consumption was significant lower in the HA PCOS group, whereas abortion rate was significantly higher and live birth rate was significantly lower in the HA PCOS group, compared with the control and non-HA PCOS groups. In the HA PCOS group, the number of available embryos tended to be higher with no significance. The GnRH-antagonist protocol is more suitable for HA PCOS patients, with lower cost and more number of embryos available for transfer. Due to the high abortion rate and low live birth rate, a freeze-all approach might be a preferable option for HA PCOS patients so as to create a buffer for reducing androgen levels before transferring freeze-thawed embryos.     

Ovarian sensitivity index is a better measure of ovarian responsiveness to gonadotrophin stimulation than the number of oocytes during in-vitro fertilization treatment

Purpose

To validate the use of the ovarian sensitivity index (OSI) as a measure of ovarian response during in-vitro fertilization (IVF) treatment.

Methods

This is a retrospective study carried out in an assisted reproduction unit in a teaching hospital. We analysed data from 2,556 women undergoing the first IVF cycle between 2002 and 2009. OSI was calculated as the number of retrieved oocytes divided by total dose of FSH administered (per 1,000 IU). Its correlation to other parameters of ovarian response was compared to that of the oocyte number.

Results

The correlation coefficients of OSI with age, AFC, AMH, total dose of gonadotrophin, average daily dose of gonadotrophin and duration of stimulation were significantly higher than that of oocyte number with these respective parameters. OSI demonstrated a higher intraclass correlation coefficient (ICC) than the oocyte number when comparing the two parameters across the first and second stimulated IVF cycles.

Conclusions

OSI is a better measure of ovarian responsiveness to gonadotrophin stimulation than the oocyte number, and is particularly useful when different subjects are treated with different stimulation regimens which would have confounding effect on the oocyte number.     

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups.     

Heterotopic pregnancy at 16 weeks of gestation after in-vitro fertilization and embryo transfer

We present an heterotopic pregnancy at 16 weeks of gestation following IVF/ ET treatment with the ectopic pregnancy located in the left fallopian tube. Intra-abdominal bleeding secondary to an heterotopic pregnancy, causing acute abdominal pain and hemorrhagic shock, should be included in the differential diagnosis even in the second trimester of pregnancy, especially in patients, achieving conception with the use of assisted reproduction techniques. Received: 20 July 2000 / Accepted: 10 April 2001     

In vitro fertilization outcomes in patients experiencing a premature rise in luteinizing hormone during a gonadotropin-releasing hormone antagonist cycle

Patients undergoing controlled ovarian hyperstimulation and pituitary suppression with a GnRH antagonist who experienced a transient premature rise in LH were compared with those who did not have an early surge. Those experiencing a premature LH surge had equivalent clinical and ongoing pregnancy rates per ET.     

The influence of estradiol/follicle and estradiol/oocyte ratios on the outcome of controlled ovarian stimulation for in vitro fertilization

Objective. The aim of the study was to evaluate the influence of the ratios of estradiol (E₂) to either the number of follicles >14 mm on the day of human chorionic gonadotropin administration (E₂/follicle) or the number of oocytes retrieved (E₂/oocytes) during controlled ovarian hyperstimulation (COH) with gonadotropin-releasing hormone (GnRH)-agonist (agonist group) and GnRH-antagonist (antagonist group), on the outcome of in vitro fertilization (IVF) cycles.

Patients and methods. All consecutive women aged <35 years admitted to our IVF unit during a 6-year period with normal to high response to COH were retrospectively studied. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred and pregnancy rate were assessed.

Results. Six hundred and ninety consecutive IVF cycles were evaluated, 301 in the agonist group and 389 in the antagonist group. The ratios of E₂/follicle and E₂/oocyte were significantly higher in the agonist group (p < 0.001 for both). Moreover, while pregnancy rates within E₂/oocyte ratio of 100–200 pg/ml were comparable between the agonist and antagonist groups, when E₂/oocyte ratios were <100 pg/ml or >200 pg/ml, pregnancy rates were significantly higher in the agonist group. Furthermore, no difference in pregnancy rates was observed within the agonist group between different E₂/oocytes ratios, while within the antagonist group, higher pregnancy rates were observed when comparing those with E₂/oocyte ratio of 100–200 pg/ml with those with E₂/oocyte ratio <100 pg/ml or >200 pg/ml.

Conclusion. While E₂/oocyte ratio cannot predict the success of GnRH-agonist protocol, patients undergoing GnRH-antagonist protocol should reach E₂/oocyte ratio within the 100–200 pg/ml range in order to achieve the best IVF outcome.     

The impact of luteinizing hormone supplementation in gonadotropin-releasing hormone antagonist cycles: a retrospective cohort study

The impact of exogenous luteinizing hormone (LH) supplementation to patients undergoing controlled ovarian stimulation with gonadotropin-releasing hormone (GnRH) antagonists on cycle outcomes is controversial. Here, we present a retrospective cohort study including cycles from December 2015 to December 2016. Totally 320 cycles were divided into two groups according to with or without exogenous LH supplementation. No significant differences regarding the number of retrieved oocytes, the number of good-quality embryos, and clinical pregnancy rate between the two groups were found. The logistic regression analysis revealed that LH supplementation was not independently associated with clinical pregnancy rate (OR?=?0.577, 95% CI: 0.272–1.222, p?=?.58) or a biochemical pregnancy rate (OR?=?0.922, 95% CI: 0.444–1.916, p?=?.83). When patients were divided into subgroups based on age, more retrieved oocytes (5.60 vs. 3.97, p?=?.04) and good-quality embryos (3.07 vs. 1.93, p?=?.01) were achieved in cycles with exogenous LH supplementation for 40 years and over group. We conclude that for aged women (40 years old and over), LH supplementation has a positive impact on the number of retrieved oocytes and good-quality embryos in GnRH antagonist cycles.