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Comparison of fecundity after second laparotomy for endometriosis to in vitro fertilization and embryo transfer.

OBJECTIVE: To study the prognosis for conception subsequent to a second conservative laparotomy for infertile patients with moderate and severe endometriosis, compared with the reproductive outcome of one cycle of in vitro fertilization and embryo transfer (IVF-ET). MATERIAL AND METHOD: From January 1990 to February 2000, 190 infertile patients had initial conservative laparotomy for pelvic endometriosis at a university hospital. All of these patients had moderate or severe endometriosis. After the failure of the initial operation to restore fertility, 32 patients requested the second operation while 24 patients underwent one cycle of IVF-ET. The cumulative pregnancy rate after the second operation was compared with the clinical pregnancy rate after one cycle of IVF-ET. RESULT: The cumulative pregnancy rate following the reoperation was 20.5% within 1 year with no additional increase in 2 and 3 years of follow up. The clinical pregnancy rate per stimulation of one cycle of IVF-ET was 12.5%. There was no statistically significant difference (P = 0.54). CONCLUSION: Despite a trend toward a higher cumulative pregnancy rate following the second conservative laparotomy, there was no statistically significant difference, when compared with one cycle of IVF-ET in moderate and severe endometriosis-associated infertile patients who had not conceived after the initial operation.

Adult↗

Endogenous plasma growth hormone and the occurrence of pregnancies in patients undergoing in-vitro fertilization and embryo transfer with ovarian stimulation.

This study was undertaken to investigate a possible relationship between endogenous secretion of growth hormone (GH) during ovarian stimulation and treatment outcome in patients undergoing in-vitro fertilization (IVF) and embryo transfer. Plasma samples obtained from 19 women who had successfully completed all stages of IVF/embryo transfer were analysed retrospectively. Based on the increase in GH during treatment, 11 GH responders and eight GH non-responders were identified. Mean daily GH concentrations for the GH responders and GH non-responders were 3.5 +/- 1.8 and 1.8 +/- 0.8, 5.4 +/- 2.3 and 0.5 +/- 0.2, and 9.0 +/- 1.9 and 0.7 +/- 0.1 ng/ml (P < 0.05) for days 10, 11 and 12 respectively. Plasma insulin-like growth factor-I slightly increased with treatment in both groups. No significant difference between these groups was found in relation to treatment duration, number of human menopausal gonadotrophin ampoules used, oestradiol peak values, and number of oocytes retrieved or fertilization rate. Seven of the 11 GH responder women conceived in comparison with one pregnancy among eight GH non-responder patients (P < 0.05). In view of the absence of differences in the clinical and laboratory parameters, we suggest that the occurrence of pregnancies among GH responder patients might be related to a positive local effect of GH or its mediators on uterine receptivity at the time of nidation.

Adult↗

Embryonic mortality in heifers after artificial insemination and embryo transfer: differences between virgin and repeat breeder heifers.

Embryos were collected from repeat breeder heifers and virgin heifers seven days after insemination, classified and transferred to the uterine horn contralateral to the corpus luteum of synchronised inseminated recipients. Altogether 35 transfers were performed, all reciprocally between repeat breeder heifers and virgin heifers. The recipients were slaughtered either 16 to 17 days or 32 to 35 days after insemination. The survival rate of the native embryos was lower among the repeat breeder heifers than among the virgin heifers both at 16 to 17 days (six of nine vs six of six) and at 32 to 35 days (three of 10 vs seven of 10) after insemination. A higher proportion of embryos transferred from repeat breeder heifers to virgin heifers than from virgin heifers to repeat breeder heifers survived to days 16 to 17 (five of six vs two of nine), while the same proportion of embryos survived to days 32 to 35 (two of 10) in both heifer categories. The results suggest that the uterine environment in repeat breeder heifers is suboptimal for the support of normal embryonic development.

Animals↗

Changes induced in serum protein profiles by ovarian stimulation during in-vitro fertilization--embryo transfer treatment: a comparison between conception and non-conception cycles.

The profiles of plasma protein concentrations during the follicular phase in unstimulated women and in women undergoing ovarian stimulation for in-vitro fertilization--embryo transfer (IVF-ET) treatment are described. Plasma protein concentrations are correlated with those of total oestradiol (protein-bound and free) and total progesterone. In addition, 10 conception cycles and 18 non-conception cycles are compared in an attempt to identify predictors of successful treatment. Ovarian stimulation caused a significant increase in follicular phase in serum concentrations of sex hormone binding globulin (SHBG), cortisol binding protein (CBP) and insulin-like growth factor binding protein 1 (IGFBP1). In contrast no increase was observed in unstimulated cycles. Serum levels of endometrial protein PP14 decreased significantly during the follicular phase in both stimulated and unstimulated cycles. Levels of pregnancy zone protein (PZP) were more than doubled at the time of oocyte aspiration compared to the unstimulated cycles. Albumin concentrations were unchanged by the stimulation. Throughout the follicular phase, levels of SHBG were significantly higher, and total oestradiol significantly lower in women who became pregnant, than in those who did not. Therefore, a low concentration of free, biologically active oestradiol seemed to favour pregnancy, as the concentration of albumin is similar in the two groups. The endometrial protein PP14 was significantly lower during the follicular phase in conception than in non-conceptional cycles. On day 2 of the treatment cycle, the PP14 concentration showed a 75% correct prediction of conception and non-conception cycles. These results suggest that levels of PP14 may predict successful IVF cycles even before hormonal treatment is commenced.

Adult↗

Relationship between ovarian cortisol:cortisone ratios and the clinical outcome of in vitro fertilization and embryo transfer (IVF-ET).

OBJECTIVE: Previously, we have reported an association between low levels of intraovarian cortisol metabolism, mediated by 11beta-hydroxysteroid dehydrogenase (11betaHSD), and the establishment of pregnancies by in vitro fertilization and embryo transfer (IVF-ET). The objective of the present study was to investigate the relationship between the clinical outcome of IVF-ET and the intraovarian concentrations of cortisol and cortisone and the cortisol:cortisone ratios in random samples of ovarian follicular fluid (FF). DESIGN: Retrospective, double-blind correlation analyses. PATIENTS: FF samples (n = 41) were obtained from 23 women undergoing gonadotrophin-stimulated IVF-ET cycles at the Cardiff Assisted Reproduction Unit. MEASUREMENTS: Clinical pregnancy was confirmed by ultrasonography. Intrafollicular steroid concentrations were measured by radioimmunoassays. RESULTS: Concentrations of both cortisol and cortisone were significantly lower in FF samples obtained from 6 patients that conceived than in samples obtained from 17 patients that did not achieve pregnancy (cortisol (mean +/- SEM) = 304 +/- 29 vs. 407 +/- 26 nmol/l, P = 0. 0411; cortisone = 32 +/- 3 vs. 65 +/- 7 nmol/l, P = 0.0002). Intrafollicular cortisol:cortisone ratios were significantly higher in samples from conception cycles than in those samples obtained from nonconception cycles (9.7 +/- 0.7 vs. 6.9 +/- 0.5, respectively, P = 0.0060). Whereas 5 of 10 women with intrafollicular cortisol:cortisone ratios greater than the outcome-independent mean of 7.7 became pregnant, only 1 of the 13 patients with intrafollicular cortisol:cortisone ratios < 7.7 conceived (chi2 = 5. 247, P = 0.0220). CONCLUSIONS: Concentrations of both cortisol and cortisone were significantly lower in FF samples obtained from patients that conceived by IVF-ET than in those obtained from nonconception cycles. Conception by gonadotrophin-stimulated IVF-ET was associated with an elevated intrafollicular ratio of cortisol:cortisone, consistent with a low level of intraovarian cortisol oxidation by 11betaHSD.

Buserelin↗

Embryo transfer and related techniques in domestic animals, and their implications for human medicine.

This report was commissioned by the Canadian government on the relevance of new techniques in animal embryology to the social, ethical and clinical applications of assisted human reproduction. It briefly describes the history of animal breeding, and the regulation of the female reproductive tract, ovulation and fertilization in laboratory and veterinary species. Embryo transfer is described in detail, including the synchronization of reproductive cycles, superovulation and embryo growth in vitro. Methods of experimental embryology, including bisection, sexing of spermatozoa and embryos, cloning and gene therapy are described. The relevance of these studies to human IVF are considered briefly.

Animals↗

Subnormal sperm parameters in conventional semen analysis are associated with discrepancies between fertilization and pregnancy rates in in-vitro fertilization and embryo transfer.

Three hundred and twenty-eight consecutive treatment cycles in 168 couples were analysed retrospectively in order to examine the influence of conventional semen analysis results on the outcome of in-vitro fertilization and embryo transfer with respect to the occurrence of both fertilizations and pregnancies. All treatments were performed under maximally standardized and controlled conditions. Each of the three main determinants of the spermiogram, namely the concentration, motility and morphology of sperm in seminal plasma, was of significant importance for fertilization and subsequent pregnancy. Best correlations were achieved by counting the number of progressively (a+b) motile sperm and the number of normally formed sperm in seminal plasma. The pregnancy rate was reduced significantly in cases in which the sperm concentration was < 10 x 10(6) ml-1 (P < 0.01), or in which there was < 40% progressively motile sperm (P < 0.001), or < 30% normally formed sperm (P < 0.001). If more than one parameter in the spermiogram was abnormal, the fertilization rate depended mainly on the most disturbed sperm parameter. The implantation rate as well as the pregnancy rate was reduced significantly in patients with low progressive sperm motility and normal morphology rates. The difference could only be attributed partially to the lower number of embryos replaced. In conclusion, subnormal sperm quality seems to interfere with developmental stages beyond the process of fertilization.

Adult↗

Pregnancy results following embryo transfer in women receiving low-dosage variable-length estrogen replacement therapy for premature ovarian failure.

This study was undertaken to evaluate the effectiveness of a new, constant low-dose, variable-length estrogen replacement therapy in preparing the endometrium of women suffering premature ovarian failure for embryo implantation. Five of 10 patients receiving the new regime became pregnant following a total of 14 embryo transfers. This study proves the efficacy of low-dosage variable-length estrogen replacement therapy for preparing the endometrium for embryo implantation in patients suffering premature ovarian failure. These studies confirm earlier observations that sequentially increasing doses of estrogen during the follicular phase are unnecessary for implantation and that the length of the follicular phase within certain undefined limits is not critical. A second important observation arising from this study concerns the relative effectiveness of the route of administration of progesterone. Five of seven patients became pregnant after receiving vaginal pessaries, compared to none of seven following intramuscular injections.

Adult↗

Severe ovarian hyperstimulation syndrome and combined intrauterine and tubal pregnancy after in-vitro fertilization and embryo transfer.

Ovarian hyperstimulation syndrome (OHSS) and heterotopic pregnancy are two well recognized entities occurring after in-vitro fertilization (IVF). This is the first reported case of a severe OHSS and coexistent heterotopic pregnancy after IVF and embryo transfer. Diagnosis of tubal pregnancy was obscured both by stimulated ovaries which prevented accurate ultrasound definition and the coexistence of an intrauterine pregnancy which accounted for human chorionic gonadotrophin (HCG) concentrations and also for aggravation of the OHSS. The roles of transvaginal ultrasound, diagnostic laparoscopy and early paracentesis in the management of this rare complication of assisted reproductive technologies are discussed.

Adult↗

Effects of progesterone on luteinizing hormone release and estradiol/progesterone ratio in the luteal phase of women superovulated for in vitro fertilization and embryo transfer.

The present study extends the information on the effects of progesterone (P) on the luteinizing hormone (LH) release, and estradiol (E2)/P ratio in the luteal phase in women superovulated for in vitro fertilization and embryo transfer (IVF-ET). Two groups of 34 patients were induced for ovulation with clomiphene citrate and human menopausal gonadotropins. One group was given 25 mg P (Gesterol, Steris Laboratory Inc., Phoenix, AZ) at the time of, or 4 to 6 hours before human chorionic gonadotropin (hCG) administration and another group served as control (no Gesterol). Of the 34 patients in the Gesterol group, 10 had Gesterol 4 to 6 hours before the administration of hCG, 13 at the time of hCG, and 11 after the spontaneous LH surge. Administration of Gesterol 4 to 6 hours before hCG significantly increased the LH values (19.0 +/- 10.3) compared with those who had Gesterol at the time of hCG (6.8 +/- 2.8, P = 0.0006). A single dose of Gesterol (25 mg P) significantly reduced the E2/P ratio during the luteal phase (P = 0.0005). However, the outcome of IVF-ET was the same in the Gesterol and no-Gesterol groups. It is concluded that a significant increase in P triggers an LH surge and a single dose of Gesterol decreases E2/P ratio in the luteal phase of women after ovarian stimulation. The biochemical mechanisms are unclear.

Embryo Transfer↗

Monitoring of in vitro fertilization-embryo transfer cycles by ultrasound versus by ultrasound and hormonal levels: a prospective, multicenter, randomized study.

OBJECTIVE: To determine whether cycle monitoring using both serum E(2) and ultrasound findings yields superior clinical pregnancy rates during IVF-embryo transfer (ET) compared to monitoring with ultrasound alone. DESIGN: Prospective, randomized, multicenter, patient-blinded study. SETTING: Four assisted conception units in the United Kingdom. PATIENT(S): Two hundred ninety-seven women believed to be normal responders undergoing IVF treatment. INTERVENTION(S): Patients were randomly allocated on day 7 of stimulation to one of the two hCG administration criteria: [1] the E(2)-to-follicle > or =11 mm ratio was between 250 and 500 pmol/L/follicle and at least 2 follicles reached a mean diameter of 18 mm or [2] at least 2 follicles reached a mean diameter of 18 mm and the endometrium thickness was > or =8 mm. MAIN OUTCOME MEASURE(S): Duration and cumulative dose of recombinant human FSH, total number of growing follicles, oocytes retrieved, number and quality of embryos, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS) rates. RESULT(S): Two hundred ninety-seven patients were randomized to one of the two criteria groups. Of these, 288 (97%) received urinary (u)-hCG (143 in group A and 145 in group B). One hundred three women in group A (72%) met both criteria for hCG administration. Pregnancy and OHSS rates were similar (34.3% vs. 31.4% and 4.9% vs. 4.1%, respectively). CONCLUSION(S): The addition of E(2)/follicle criteria to ultrasound monitoring of IVF cycles in normal responders seldom changes the timing of hCG, and does not increase pregnancy rates or the risk of OHSS.

Adult↗

[Impact of high response of ovary to gonadotropin stimulation on the outcome of in vitro fertilization and embryo transfer or intracytoplasmic sperm injection].

OBJECTIVE: To evaluate the impact of elevated peak estradiol (E(2)) levels and a high number of retrieved oocytes on implantation and pregnancy rate in patients undergoing in vitro fertilization-embryo transfer (IVF-ET) and intracytoplasmic sperm injection (ICSI). METHODS: Retrospectively analyzed 474 infertile women undergoing 510 cycles for IVF-ET/ICSI treatment during the period of March 1999 to December 2000. Using a standard long protocol/flare-up protocol [(gonadotropic hormone releasing hormone agonist/high pure follicle-stimulating hormone (FSH-HP)/human chorionic gonadotropin (hCG)] for ovarian stimulation. High responders were defined as those who had peak E(2) levels of > 11 010 pmol/L on the day of hCG administration (n = 160) or > 15 retrieved oocytes (n = 148). Normal responders were defined as those who had peak E(2) levels of </= 11 010 pmol/L on the day of hCG administration (n = 350) or </= 15 retrieved oocytes (n = 362). RESULTS: There were statistically significant differences in age, infertile years, basal FSH level and the ampules of FSH-HP required between high and normal responders (P < 0.01 and P < 0.05). Ovarian hyperstimulation syndrome (OHSS) increased significantly in the high responders (P < 0.01). There were no statistically significant differences in implantation rate or pregnancy rate between high and normal responders. CONCLUSION: Elevated peak E(2) levels and high oocytes retrieved were not detrimental to IVF outcome, but had high incidence of OHSS.

Adult↗

Investigation of staff and patients' opinions of a proposed trial of elective single embryo transfer.

BACKGROUND: In the context of mounting concern about the risks of twin pregnancies resulting from IVF, this study aimed to assess staff and patients' attitudes towards a proposed randomized controlled trial (RCT) of elective single embryo transfer (SET) in a Scottish fertility centre. METHODS: The views of 10 members of IVF clinic staff were assessed by means of a focus group and those of 12 couples by semi-structured interviews. RESULTS: Staff were aware of the risks of twin pregnancies to mothers and babies and the need for evidence of success in SET, but had reservations about the proposed RCT. The need to subject patients to unpopular scientific procedures such as randomization and blinding conflicted with their perceived caring role. They felt it would be hard to recruit and onerous to patients but nevertheless discussed how it could be successfully mounted if necessary. They debated how to ensure that consent was fully informed, and when, and how, to randomize. Patients accepted the possibility of twins but were largely unaware of risks inherent in twin pregnancies. They saw no need for a trial and found the idea of randomization unacceptable except in younger women. They would accept SET if it became unit policy and appeared unaffected by financial considerations. CONCLUSIONS: Involving affected staff at the design stage may make it easier to conduct a SET trial in their clinics. IVF patients whose ultimate goal is pregnancy are less likely to support a trial which aims to minimize twin pregnancies.

Adult↗

The technique for human embryo transfer at Tygerberg Hospital.

From 1 May 1984 to 30 April 1985 177 laparoscopies were performed; 684 oocytes were obtained and a fertilization rate of 85% per oocyte achieved. There was a pregnancy rate of 24.3% per embryo transfer (ET) and 20.9% per laparoscopy after 152 patients were subjected to ET. The ET technique at Tygerberg Hospital, using the Tomcat catheter, is described. An introducer--the FT introducer--designed to overcome technical difficulties in selected patients in passing the Tomcat catheter is described. Technical problems are easily overcome with this introducer. In 26 patients (17.1%) ET was performed using this instrument and 8 pregnancies resulted (a pregnancy rate of 30.7% per ET). This pregnancy rate indicates the value of the instrument.

Adult↗

Are implantation and pregnancy outcome impaired in diethylstilbestrol-exposed women after in vitro fertilization and embryo transfer?

Forty-six infertile women with a history of diethylstilbestrol (DES) exposure in utero underwent 149 stimulation attempts for in vitro fertilization (IVF). The mean (+/- SE) number of preovulatory oocytes harvested at retrieval and transferred was 3.9 +/- 3.3 (536/138) and 2.6 +/- 1.4 (328/124). When compared with patients with tubal factor infertility and less than or equal to 4 pre-embryos transferred, the clinical pregnancy rate (15.3% versus 22%) was not statistically different. However, the term/ongoing pregnancy rate was significantly lower in the study group (8% versus 16%). Comparison of the IVF outcome with different uterine anomalies as detected by hysterosalpingogram (n = 29) showed a trend for a worse prognosis in women with constrictions and a combination of T-shape and constrictions. It is concluded that implantation and pregnancy outcome are impaired in DES-exposed women after IVF.

Adult↗

Evaluation of the quality of porcine somatic cell nuclear transfer embryo by gene transcription profiles.

This study aimed to evaluate the quality of porcine somatic cell nuclear transfer (SCNT) embryos by examining its gene transcription patterns. Embryos were produced by SCNT, intracytoplasmic sperm injection (ICSI) or under different conditions, and transcripts of genes for fibroblast growth factor receptor (FGFr) 2IIIc, FGFr72IIIb, X inactive-specific transcript (Xist), interleukin 6 (IL6), IL6 receptor (IL6r) alpha and c-kit ligand, were detected by real-time RT-PCR. The percentages of embryos in which these transcripts were detected were similar in SCNT and ICSI embryos. On the other hand, the transcriptional levels of the FGFr72IIIb and IL6ralpha genes were 0.5 times less and 2 times more, respectively, in SCNT blastocysts than those of ICSI blastocysts (p<0.05). When nuclear transfer was performed before or after activation of oocytes, embryos in the latter case showed significantly lower frequencies of having FGFr72IIIb (74% vs. 90%) and Xist (3% vs. 33%) transcripts compared to the former case embryos (p<0.05). When two lines of nuclear donor cells with different developmental potencies were used, the transcriptional profiles in the reconstructed embryos did not show any significant differences. Our study suggests that expression profiles of FGFr72IIIb, IL6ralpha, and Xist can be used as markers for the diagnosis of the developmental potency of porcine nuclear transfer embryos.

Animals↗

Assessment of follicular maturity by follicular diameter and fluid volume in a program of in vitro fertilization and embryo transfer.

We compared the assessment of follicular maturity by follicular diameter or follicular fluid (FF) volume and the subsequent fertilization and cleavage of the oocytes in 36 patients who had ovarian stimulation performed for in vitro fertilization and embryo transfer (IVF-ET). All patients received clomiphene citrate and human menopausal gonadotropin. The daily growth of follicles was assessed ultrasonically for 6 consecutive days before oocyte collection. The follicular diameter was found to be well correlated with the volume of follicular fluid. There were no significant differences among the dominant, second, and third follicles in the rates of oocyte recovery, maturation, fertilization, or cleavage. The rates of oocyte maturation and fertilization in FF volumes of 5.1 to 7.0 ml were significantly higher than in volumes of 1.1 to 5.0 ml, but the cleavage rates were similar. A smaller percentage of embryos developed to the four-cell stage when the oocytes were recovered from follicles with volumes of 1.1 to 3.0 ml. These observations suggest that follicular volume is a good parameter for judging the maturity of oocytes. It is also suggested that, although the oocytes of small follicles can be fertilized and cleaved, oocytes from larger follicles may have a better developmental capacity.

Embryo Transfer↗

In vitro fertilization and embryo transfer at North Shore University Hospital: initial experiences.

No technical difficulties were encountered in visualizing follicles and obtaining aspirates at laparoscopy. At least one oocyte was aspirated in 90% of these women. While the majority of eggs inseminated subsequently cleaved (73%), no pregnancies occurred despite seemingly atraumatic embryo transfer in nearly all women. As two pronuclei were visualized in the majority of cases, one cannot invoke polyspermy as a cause of failure of subsequent embryo development; nor is it possible at this time to segregate those abnormalities in the egg, at the time of oocyte retrieval, from those encountered by normal preimplantation embryos in an abnormal uterine environment, perhaps secondary to hormonal aberrations coincident with gonadotropin stimulus.

Embryo Transfer↗