Ovarian cyst aspiration prior to initiating ovarian hyperstimulation for in vitro fertilization

Twenty-three consecutive patients presenting for in vitro fertilization were evaluated with transvaginal sonography on cycle day 3, prior to initiating ovarian hyperstimulation. Three of these patients were noted to have large ovarian cysts. All three underwent transvaginal aspiration of the cysts, followed immediately by initiation of ovarian hyperstimulation. Following oocyte retrieval, in vitro fertilization, and embryo transfer, all three women achieved pregnancy. We conclude that cyst aspiration is not contraindicated when an ovarian cyst is encountered in the follicular phase of an in vitro fertilization cycle.     

The relationship of semen parameters to fertilization in patients participating in a program of in vitro fertilization

Approximately 80% of the patients in a program of in vitro fertilization (IVF) will fertilize an oocyte. The purpose of this study was to determine which parameters of the semen analysis influence fertilization in vitro. Of 120 patients participating in an in vitro fertilization program, 98 achieved fertilization of at least one mature oocyte and 22 did not. Ovulation induction was standardized and patients whose sperm was exposed to at least one mature oocyte (by light microscopy) were included in the study. Semen washing was accomplished using a swim-up technique. Semen parameters were assessed both before (raw) and after washing. Following insemination with 100,000 motile sperm, fertilization was determined by the presence of pronuclei or cleavage. Mean sperm count and motility were higher in patients who fertilized. However, morphology was similar. Fertilization was more likely to occur with a raw density>104 million/ml and a motility>64%, as well as with a density>18 million/ml and a motilkity>86% following washing. Furthermore, washing lowered sperm counts by 75% and increased motility by 25% but had no effect on morphology. This study demonstrates that sperm count and motility, but not morphology, influence fertilization in a program of in vitro fertilization and that patients with higher counts and motility have and greater probability of fertilization.Presented at the Third Annual Congress of Andrology, April 27–May 2, 1985, Boston, Massachusetts.     

Use of follicle-stimulating hormone (FSH) to increase the in vitro fertilization (IVF) efficiency of mice

Purpose The possibility of increasing the efficiency of an in vitro fertilization system (IVF) for Swiss OF1 mice was studied. The experimental protocol proposed analyzed the use of FSH as a superovulatory inducing hormone in comparison to traditional PMSG treatment. At the same time, the quality of IVF-derived embryos was evaluated both in vitro, with culture in CZB medium and fixation in advanced stages of development, and in vivo, by transfer to female recipients.Results Treatment with FSH induced a much higher ovulation number compared to PMSG (64.26 vs 33.85; P<0.01). With this gonadotropin, IVF provided a positive tendency to normal fecundation (67.76 vs 64.72; P<0.1) and a much lower index of abnormal division in embryos (10.57 vs 15.11; P<0.05). The viability of embryos obtained from donors treated with hormones was similar, although differences did exist regarding embryo origin: those obtained following natural fertilization showed a higher developmental capacity both in vitro (P<0.05) and in vivo (P<0.05).Conclusions We conclude that FSH is an improved superovulation alternative treatment in comparison to PMSG for IVF. It provides a higher number of embryos with the same in vitro and in vivo viability as those obtained from PMSG.     

体外受精-胚胎移植技术中74例异位妊娠的临床分析

目的:分析体外受精-胚胎移植(in vitro fertilization and embryo tranfer,IVF-ET)助孕技术中发生异位妊娠的影响因素、诊断、治疗方法及预防措施。方法:回顾性分析IVF-ET助孕技术中发生异位妊娠74例患者的临床资料。结果:所有接受IVF-ET的1 585患者中,共发生异位妊娠74例,异位妊娠发生率为4.67%;异位妊娠类型中输卵管妊娠71例,占总异位妊娠的95.95%。新鲜胚胎移植周期组异位妊娠发生率(5.41%)显著性高于冷冻胚胎复苏移植(frozing embryo transfer,FET)周期组(2.35%)(P<0.05)。移植深度距离宫底>1.2 cm时异位妊娠发生率显著性低于移植深度0.8~1.2 cm组。结论:IVF-ET助孕技术中异位妊娠发生率较自然妊娠过程中高;输卵管因素、促排卵药物的应用以及胚胎移植的深度是异位妊娠发生的主要影响因素。     

Unsuccessful in vitro fertilization: A follow-up study

Results from a follow-up questionnaire completed by 28 women who had unsuccessfully completed one or more trials of in vitro fertilization (IVF) are reported. The mean time lapse since completing IVF was 8.4 months. During that period, 33% of the respondents had applied for adoption and 11% had secured an adoptive child. More than half the respondents had abandoned biological attempts to conceive and 52% felt as though they had resolved the infertility crisis. Nevertheless, 93% of the respondents indicated that they would participate in any new reproductive options that would enhance the likelihood of a biological pregnancy! The results and implications of this study are discussed.     

Ultrasonic detection of a cumulus oophorus in patients undergoing in vitro fertilization

Ultrasonic studies for the detection of a cumulus oophorus were carried out in 57 women taking part in an in vitro fertilization (IVF) program. When intrafollicular echoes were dissociated, clearly prominent from the follicular wall, they were considered to be a sure cumulus mass, and when they were only slightly prominent, they were suspected to be a nondissociated cumulus. All patients had at least one ultrasonically visible cumulus. A cumulus was seen in 50% of the follicles and 70% of them were dissociated. Cumuluses were also seen in follicles <18 mm in diameter but a significantly higher number of them were not clearly dissociated. The number of observed dissociated cumuluses correlated significantly with the number of recovered mature oocytes. However, in 18 patients there were more mature oocytes retrieved than cumuluses identified by ultrasound. When a cumulus mass is seen, it can be taken as evidence of a sign of maturity of that particular follicle and oocyte. However, mature oocytes are also found where no cumulus was seen by ultrasound. Lack of visible cumulus has little significance in predicting the maturity of the oocyte.     

Inherent sources of ultrasound variability in relation to follicular measurements

Determination of ovarian follicular size and number by real-time ultrasound lacks the precision that has been ascribed to it. Four major error sources inherent in the scanning and interpreting process were analyzed to determine the relative contributions to overall variation. The sources measured were machine, sonographer, sonologist, and patient bladder volume. A protocol using a normal clomiphene-stimulated woman allowed the determination of the coefficient of variance for both follicular number and follicular diameter as well as a mean diameter range in each of the categories. A large degree of variation was found in all groups. Surprisingly, it was noted that maximal bladder filling did not produce optimal images. We believe that while variability in ultrasound can be recognized and lessened, it cannot be eliminated. Thus, caution must be used when ultrasound follicular comparisons are made within each program from day to day and particularly between institutions. A liberal range should be allowed for optimal follicle sizes for any given stimulation protocol.     

Ultrasonic assessment of endometrial changes in stimulated cycles in an in vitro fertilization and embryo transfer program

Four distinct patterns in the ultrasonic appearance of preovulatory endometrium can be identified and described in patients undergoing stimulated cycles in an in vitro fertilization program. Ultrasonically, this endometrial response can be seen as a quantitative change in thickness and a qualitative change in gray-scale appearance or reflectivity. The application of this additional parameter of endometrial assessment together with the conventional measurement of follicular diameter as a means of optimally timing oocyte collection has been associated with a reduction in the preoperative ovulation rate from 10.9 to 3.2%, an increase in the fertilization rate from 59.2 to 82.5%, and in a pregnancy rate per embryo transfer of 20.5% in our program without the use of hormonal assays.     

A model to show human uterine receptivity and embryo viability following ovarian stimulation for in vitro fertilization

A comparison of the implantation rates following in vitro fertilization (IVF) and embryo transfer (ET) for four major groups indicates differences in the implantation rates as well as in the incidence of multiple implantation. By assuming that the probability of implantation is the product of two variables, uterine receptivity (U) and embryo viability (E), estimates for U and E are derived for each of the four (VF groups using maximum likelihood methods. The UE model is tested using chi-squared goodness-of-fit methods for predicted implantation rates versus observed. The possibility that differences in U values between groups are due to different ovarian stimulation protocols is discussed, as is the values of the UE model in highlighting differences between IVF groups and its importance in predicting multiple pregnancy rates.     

Ultrasound as a diagnostic and operative tool for in vitro fertilization and embryo replacement (IVF/ER) programs

Diagnostic ultrasound offers unique possibilities to study ovarian morphology, especially follicular growth and development. This makes the technique an important tool for the management of ovulation induction in an in vitro fertilization and embryo replacement (IVF/ER) program. Different general aspects of the use of ultrasound in IVF/ER are discussed in this communication.     

A formula for scoring human embryo growth rates in in vitro fertilization: Its value in predicting pregnancy and in comparison with visual estimates of embryo quality

Two systems for measuring embryo development in vitro were evaluated. One was a 1–4 scale based on a subjective evaluation of embryo quality (EQ) from microscopic appearance. In addition, a formula for scoring embryo growth rate in vitro was developed. The embryo development rating (EDR) was based on the ratio between the time at which embryos were observed at a particular stage after insemination and the time at which they would be expected to reach that stage in a hypothetical ideal growth rate with a cell cycle length of 11.9 hr. Using this scoring system, normally growing embryos scored 100. This approach was aimed at partially normalizing the data and allowed all embryos to be analyzed similarly regardless of the time of observation. Analysis of 1539 embryo replacements resulting in 232 clinical pregnancies showed that both EDR and embryo-quality scores were of value in predicting success, with clinical pregnancy most likely to eventuate from a combination of moderate to good EQ scores (2–4) coupled with average or above-average growth rates (EDR scores from 90 to 129). Poor-quality and very slowly or very rapidly growing embryos were underrepresented in cycles that proceeded to pregnancy. These inferences were based on all embryos transferred (mean, 2.73 per transfer cycle), and they were substantiated by an analysis of 33 pregnancies resulting from replacement of a single embryo and from 18 pregnancies in which all embryos scored the same with both systems. EQ and EDR were significantly associated with each other and together provide a valuable guide in predicting pregnancy, in selecting embryos for freezing, and in monitoring day-to-day performance in the in vitro fertilization (IVF) program.     

A microcomputer data base system for an in vitro fertilization clinic programmed in BASIC

A computer program was developed for the IBM personal computer to be used for in vitro fertilization and gamete intrafallopian transfer clinics. This program, written in BASIC, allows input, editing, updating, sorting, and printing of patient data. Statistical functions permit summation of patient data based on various combinations of user-defined treatment cycles, diagnoses, and protocols, thus making possible comparison of pregnancy and other patient data between and among various treatment groups and diagnoses. The statistical information can be continually updated and revised when new data become available on patients (such as confirmation of pregnancy by ultrasound or live births) and at the end of each cycle. The formats used are useful in assimilating individual clinic data for various surveys and other reporting requirements. The program can be easily modified by anyone with minimal training in the BASIC programming language.     

Cytotoxic sperm antibodies and in vitro fertilization of mature oocytes: A preliminary report

The fertilization rates of mature oocytes during in vitro fertilization and embryo transfer (IVF-ET) using fetal cord serum-supplemented insemination media were 57% for five infertile couples without sperm antibodies (group 1). But they were 50% for four of nine infertile couples (group 2) with cytotoxic sperm antibodies in both partners (n=6) or the husband alone (n=3). Two women in group 1 were successful in achieving normal, full-term pregnancies with the delivery of normal infants (²=4.2, P < 0.05, by chi-square analysis). One of them consistently tested negative for sperm antibodies, while her husband was previously treated with antibiotics for infection and transient sperm antibodies in the seminal plasma. Subsequently, antibody liters in the husband were in the normal range when the successful IVF-ET was performed. One woman in group 2, with antibodies to her autoimmune husband's sperm but not control sperm and with a long-standing poor postcoital test sperm motility, conceived through artificial insemination with donor sperm (AID) after failing to conceive with her husband through IVF-ET. These data suggest that the presence of cytotoxic sperm antibodies in the serum and/ or secretions of both partners reduces the rates of fertilization of mature oocytes in spite of using fetal cord serum in the IVF media. Pregnancy achievement is impaired in this group.     

In vitro fertilization and embryo replacement at the department of obstetrics and gynecology,University of Kiel,F.R.G.

From July 1982 until September 1983, 194 pelviscopies were performed in Kiel (phase I). The patients were stimulated either with Clomidlhuman menopausal gonadotropin (hMG)/human chorionic ganadotropin (hCG) or with Clomid/hCG or hMG/hCG alone. Follicular maturation was monitored by ultrasonography and the daily measured E₂ and luteinizing hormone (LH) response. Surgic therapeutical pelviscopy with follicular puncture followed 36 hr after hCG application. Oocytes were incubated in either Ham's F-10 or Menezo B₂ medium in an automatically gas-controlled exsiccator. Forty-eight hours after insemination normal-looking four- to eight-cell embryos were replaced into the uterine cavity. Oocytes were successfully collected in 87.4% of the patients, with an average of 2.2 oocytes per patient. Eighteen pregnancies resulted of 101 embryo replacements. The overall pregnancy rate was 16.2% per replacement and 9.3% per pelviscopy. Undivided oocytes and polyploid embryos were analyzed cytogenetically. From October 1983 to October 1984 the overall pregnancy rate after 144 pelviscopies and 88 embryo replacements (phase II) improved to 23.9% per replacement and 14.6% per pelviscopy.     

Preimplantation development following in vitro fertilization of mouse oocytes: Effects of timing of superovulation and preincubation in vitro

The early embryonic development of in vitro fertilized oocytes was assessed following superovulation in F₁ hybrid C57BL/6×CBA/Ca mice. Decreasing the time interval between the administration of constant doses of pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) resulted in decreases in the frequency of development to the blastocyst stage but had no significant effect on development to the two-cell stage. Preincubation of postovulatory oocytes in vitro prior to insemination did not compensate for the reduced preovulatory development in vivo but resulted in decreases in the frequency of development to the blastocyst stage. The results indicate that inadequate preovulatory development of superovulated mouse oocytes can adversely affect the preimplantation development of in vitro fertilized embryos in the absence of a visible inhibitory effect on development to the two-cell stage and also that preincubation of postovulatory oocytes in vitro prior to fertilization reduces subsequent developmental capacity.     

A randomized trial of laparoscopy and transvaginal ultrasound-directed oocyte pickup for in vitro fertilization

Ninety-four (94) couples undergoing IVF for the usual spectrum of clinical reasons and who were suitable for either laparoscopic or vaginal ovum pickup (OPU) were randomly assigned at the commencement of 166 treatment cycles to one of two OPU procedures. Both patient and clinician were informed of the allocation. If either wished to change this, then that cycle was eliminated from the trial. After a period of 15 months, 103 cycles were appropriate for analysis, of which 64 had been subject to ultrasound and 39 to laparoscopic OPU. Patients in the two groups did not differ significantly in terms of are or diagnosis, and the treatment cycles did not differ significantly in terms of stimulation used, commencing or maximum estradiol (E₂) concentrations, E₂ per follicle aspirated, or characteristics of the semen used for IVF. The rate of oocyte recovery (number of oocytes obtained per follicle aspirated), the average number of embryos available for transfer, and the pregnancy rate per oocyte recovery procedure did not differ significantly in the two groups. Ovum recovery for IVF using vaginal aspirations and ultrasound guidance is as efficacious as that which uses laparoscopy.     

Transvaginal sonographically controlled ovarian puncture for oocyte retrieval for in vitro fertilization

Two hundred twenty-two patients took part in a trial of follicle puncture via the transvaginal route under sonographic control for the purpose of in vitro fertilization (IVF). Induction protocols were mainly human menopausal gonadotropin (hMG)+human chorionic gonadotropin (hCG) and clomiphene + hMC + hCG. In 79.7% oocyte aspiration could be achieved without difficulty via the transvaginal route. An average number of 4.7 oocytes per attempt was obtained: 10.7% evolutive pregnancies were obtained. No major incident was noted. This technique offers several crucial advantages: it reduces surgical risk, reduces the length of the patient's stay in hospital as well as the overall cost of the procedure, and it also makes possible puncture in some cases hitherto regarded as excluded.     

Double transfer of embryos in in vitro fertilization,or is there a delayed receptivity of the endometrium?

Sixty-seven in vitro fertilization (IVF) patients who underwent ultrasonically guided oocyte pickup (OPU) after induction of superovulation with human menopausal gonadotropins were submitted to two different protocols of embryo transfer. In the first group of 33 patients, four to five embryos were transferred to the uterus 48 hr after OPU. In the second group of 34 patients two to three embryos were transferred at 48 hr after OPU and two other embryos were transferred after freezing and thawing 48 hr later (96 hr after OPU). The pregnancy rate achieved in the double embryo transfer (ET) protocol was significantly higher than in the single-ET protocol (32.4 vs. 18.2%, respectively; P<0.05).     

The effect of endometriomas on in vitro fertilization outcome

To determine the effect of ovarian endometriomas on in vitro fertilization (IVF) outcome, two groups of patients were studied. Group I consisted of seven patients with ovarian endometriomas and severe pelvic adhesions treated for a total of 12 cycles. Group II patients consisted of eight patients with hydrosalpinges and comparable pelvic adhesions treated for a total of 27 cycles. There were no differences in the number of days required for stimulation or in the serum estradiol levels attained between the two groups. Group I patients were noted to have significantly fewer preovulatory follicles (1.42 vs 3.33,P<0.005), cycles with fertilization (28 vs 84%,P<0.005), and embryos transferred (0.78 vs 2.56,P=0.01) than Group II patients. Three pregnancies occurred in Group II, while there were no conceptions among Group I patients. This study suggests that the presence of an ovarian endometrioma(s) has an adverse effect on IVF outcome and suggests that patients with ovarian endometriomas should have them removed prior to undergoing IVF.Presented in part at the 44th Annual Meeting of the American Fertility Society, Atlanta, Georgia, 1988.     

Human amniotic fluid for fertilization and culture of human embryos: Results of clinical trials in human in vitro fertilization (IVF) programs

We report the outcome of clinical trials carried out in two IVF programs, comparing the use of human amniotic fluid (HAF) as a complete medium to Whittingham's T6 medium containing human serum T6+10% HS) for egg incubation, insemination, embryo culture, and embryo transfer. There were no significant differences in the clinical trials between HAF used alone as a complete medium and T6+10% HS in fertilization rates of eggs, cleavage rates of embryos up to 48 hours in culture, pregnancy success rates after embryo replacement or the outcome of pregnancies. There was no advantage in using T6+10% HS for fertilization of eggs and HAF as a complete medium for embryo culture and transfer in any of the parameters examined. We conclude that HAF does not meet the complete requirements of human eggs and embryos in vitro and further developments of culture media are required to obtain embryo development equivalent to that in vivo.