Placental pathology and pregnancy outcomes in donor and non-donor oocyte in vitro fertilization pregnancies

OBJECTIVE: Intrinsically poor maternal adaptation to pregnancy and dysregulated processes have been postulated to occur as a consequence of an immune response to the feto-placental unit as "foreign" material. The aim of our study was to compare placental pathology and pregnancy outcomes of in vitro fertilization (IVF) pregnancies conceived by donor oocytes with those conceived by non-donor oocytes. STUDY DESIGN: We conducted a retrospective, case-control study on 91 placentas from IVF pregnancies (36 from donor oocytes and 55 from non-donor cycles). All placentas were examined by a single pathologist for signs indicative of an immune response, including chronic villitis, chronic deciduitis, increased perivillous fibrin, ischemic change/infarction, decidual vasculopathy, increased syncytial knots, intervillous thrombi, and retroplacental hematomas. RESULTS: Placentas from donor cycles were significantly more likely to demonstrate certain pathologic findings: chronic villitis (P<0.001), chronic deciduitis (P=0.034), increased perivillous fibrin (P=0.001), ischemic change/ infarction (P=0.001), and intervillous thrombi (P =0.008). There was no statistical significance with respect to decidual vasculopathy, increased syncytial knots, or retroplacental hematomas. CONCLUSION: Pathologic evidence of an immune-mediated process is much more pronounced in donor oocyte IVF pregnancies compared to non-donor cycles. Clinical implications of these findings have yet to be determined.     

Defective oocytes: a new subgroup of unexplained infertility.

OBJECTIVE: To define a new category of unexplained infertility and its potential treatment. DESIGN: Normal infertile couples underwent prospectively, cross-fertilization attempts in which the wife's oocytes were inseminated by the husband and donor semen. After recurrent failure of fertilization, cross insemination of donor oocytes was attempted with the husband sperm. SETTING: In vitro fertilization unit at a teaching hospital. PATIENTS: Three couples who were diagnosed as suffering of unexplained infertility and treated by in vitro fertilization (IVF). RESULTS: The female partner of these couples produced morphologically normal oocytes that were demonstrated to be functionally defective and failed to fertilize in vitro with both husband and donor sperm. Donated oocytes inseminated by the husband's sperm were fertilized in all patients, demonstrating the normal fertilizing ability of the husbands' semen. One patient conceived and delivered after an oocyte donation. CONCLUSIONS: Conclusive diagnosis of defective oocytes as a cause of infertility may be made only after IVF and oocyte donation.     

Fresh versus frozen thawed semen for initial and late insemination in IVF cycles.

Frozen thawed semen has been associated with reduced semen quality and as a result diminished pregnancy rates. In vitro fertilization (IVF) can supply the true measure of the functional fertilizing capacity of fresh versus frozen-thawed semen. One hundred and six patients in an IVF program who underwent donor insemination were divided into two groups. Group I included 51 women in whom initial insemination with donor fresh or frozen semen was performed. They were compared to 65 group II women in whom late insemination with donor fresh or frozen semen was performed after initial insemination with husband semen had failed to fertilize the eggs. There was no statistically significant difference between groups I and II on initial insemination; however, statistically significant difference in fertilization (P less than 0.006) and pregnancy rates (P less than 0.001) between the two groups were achieved when late insemination was carried out. Consequently, we prefer initial insemination with frozen-thawed donor semen in cases indicated.     

Pregnancy rates in sequential in vitro fertilization cycles by oocyte donors(1)

OBJECTIVE: To evaluate the clinical outcome of in vitro fertilization (IVF) treatment cycles from individual oocyte donors who underwent multiple sequential donations. METHODS: We reviewed clinical outcome data from sequential anonymous oocyte donation cycles using donors who underwent multiple IVF stimulations. Donors were grouped by the interval between cycles and the cycle number (rank). The primary outcome measure was delivery rate by individual donor per retrieval from the combined derivative fresh and frozen embryo transfers. RESULTS: Duration and amount of gonadotropin therapy and the fertilization rates did not correlate significantly with the interval between cycles or cycle rank. Cumulative delivered pregnancy rates for cycles 1-6 were 51.5%, 54.6%, 50.5%, 51.5%, 51.1%, and 57.6%, respectively. Delivered pregnancy rates did not vary by interval between cycles. CONCLUSION: Young healthy presumed or proven fertile women can reliably donate oocytes for at least six cycles with the expectation of consistently high pregnancy rates.     

High pregnancy rate after early human embryo freezing

Human embryos produced by in vitro fertilization (IVF) were frozen with 1,2-propanediol as a cryoprotectant. Embryo survival after thawing was related to the presence of a nucleus in frozen cells and decreased with the increasing number of cells in the frozen embryo. None of five embryos frozen 3 or 4 days after IVF survived when thawed. Of 48 early embryos (35 patients) frozen 1 or 2 days after IVF, 42 (87.5%) were transferred in 32 patients. Ten pregnancies were initiated after frozen embryo transfer (ET). If we exclude the three infertile patients who had sexual intercourse in the fertile period, the pregnancy rate for each patient who had 1- or 2-day frozen embryo(s) was 22% (7 of 32). One of the pregnancies was obtained after ET of a 1-cell pronucleated frozen and thawed embryo. The rate of ongoing pregnancies after triple fresh ET was 23%. In patients having four embryos obtained in a single IVF cycle, the expected overall liveborn rate in an IVF-ET program including embryo cryopreservation could theoretically equal that of natural human fertility.     

Cryopreserved sibling oocytes and intracytoplasmic sperm injection rescue unexpectedly poor fertilization in conventional in vitro fertilization

PURPOSE: To report a successful pregnancy from cryopreserved sibling oocytes and intracytoplasmic sperm injection (ICSI) for an infertile couple with an unexpectedly low fertilization rate in the fresh in vitro fertilization (IVF) cycle. METHODS: The woman had bilateral tubal obstruction and polycystic ovarian syndrome. The man had normal semen parameters. The couple underwent a cycle of controlled ovarian hyperstimulation in that 20 oocytes were retrieved. Twelve oocytes were conventionally inseminated and eight were cryopreserved using a slow freezing method. However, only one oocyte was fertilized, and no pregnancy was achieved. In the next cycle, the frozen oocytes were thawed and ICSI was performed. RESULTS: After thawing, seven oocytes (88%) survived and one was damaged. Six were at the metaphase II stage and were injected. Five (83%) achieved normal fertilization, and all of them cleaved (100%). After replacement of the embryos, a singleton pregnancy developed. A healthy female baby was delivered at term. Karyotyping revealed 46, XX. CONCLUSIONS: In addition to well-known indications, cryopreservation of excess sibling oocytes for patients receiving IVF has a possible advantage of preventing unexpectedly low fertilization rate or fertilization failures.     

Biochemical screening for aneuploidy in patients with donor oocyte pregnancies compared with autologous pregnancies

Abstract

Objective: The objective was to determine if the rate of abnormal biochemical markers is different in pregnancies conceived by donor oocyte versus those conceived by autologous oocytes.

Methods: This is a retrospective cohort study of patients who underwent risk assessment for aneuploidy. Pregnancies conceived by egg donation were matched with control groups who conceived using their own eggs. The primary outcomes were incidence of low PAPP-A or free bHCG in the first trimester or elevated MSAFP, free bHCG or Inhibin A, or low uE3 in the second trimester.

Results: 260 singleton gestations were identified who conceived via oocyte donor. There was a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (8% versus 2%, p?=?0.028) compared to a control group matched by maternal age. There was also a significantly higher rate of unexplained elevated MSAFP in pregnancies conceived by egg donation (7% versus 2%, p?=?0.01) compared to a control group matched by age of the egg donor.

Conclusion: Pregnancies conceived by egg donation are more likely to have an unexplained elevation in MSAFP compared to pregnancies not conceived by egg donation regardless of age. Egg donation itself is not associated with other biochemical abnormalities.     

Programmed oocyte retrieval during routine laparoscopy and embryo cryopreservation for later transfer

Fixed-schedule ovulation induction and cryopreservation of the obtained embryos was performed in women undergoing a preliminary laparoscopy for infertility investigation before possible inclusion in an in vitro fertilization program. The cycle before follicular stimulation was modified by a progestogen or an estrogen-progestogen contraceptive pill. Ovarian inaccessibility precluded follicular aspiration in four of 34 patients but at least one oocyte was obtained in 29 of the remaining 30. Although fewer oocytes were obtained in these patients than in a control group undergoing in vitro fertilization treatment, one or more embryos were obtained in 22 patients in the study group. All embryos were frozen and to date 25 embryos from 17 patients have been thawed. Embryos have been placed in 16 of the 17 patients and six pregnancies have been initiated. Three are currently ongoing, one ectopic pregnancy was recorded, and two pregnancies were classified as "chemical." Programmed oocyte retrieval and embryo cryopreservation resulted in an extra chance of pregnancy in patients undergoing a laparoscopy for infertility investigation.     

Cryopreservation of zygotes and early cleaved human embryos

Zygotes and 2- to 5-cell human embryos were frozen in 1,2-propanediol and sucrose; results of the first 50 cycles (45 patients) are presented. A total of 41 zygotes (17 attempts at thawing) were thawed, resulting in six singleton clinical pregnancies (15% per embryo; 35% per cycle), of which three delivered, one aborted, and two are ongoing. Fifty-seven cleaved embryos were thawed in 33 other cycles, resulting in four singleton and one twin pregnancy (11% per embryo; 15% per cycle), of which four delivered and one is ongoing. Depending on the cell stage, 61% to 81% of embryos survived cryostorage, but 2-cell embryos did not implant. One fifth of cryoinjury was due to the formation of cracks in the zona pellucida. The incidence of implantation was not enhanced when more than one freeze/thawed embryo was replaced, most pregnancies being obtained from single embryo replacements. At least 8% more births are expected in addition to conventional in vitro fertilization methods when the current policy of replacing three fresh embryos and freezing the remainder using this technique is applied. This method will result in two to four times more pregnancies per spare embryo, compared with other cryopreservation methods using older embryos.     

Impact of retained embryos on the outcome of assisted reproductive technologies

OBJECTIVE: To assess the impact of embryo retention in the embryo transfer catheter followed by "immediate" retransfer on pregnancy outcome in women undergoing assisted reproduction. DESIGN: Retrospective analysis of embryo transfer following in vitro fertilization. SETTING: Assisted reproductive technology practice in a university in vitro fertilization program. PATIENT(S): In vitro fertilization charts for 1,812 embryo transfer cycles representing 1,139 patients between January 1997 and March 2002 were reviewed. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rate, implantation rate, delivery rate. RESULT(S): Three embryo transfer cycles were excluded from analysis because of missing data, leaving 1,364 embryo transfers during oocyte recovery cycles and 445 embryo transfer cycles using thawed embryos. Seventy-one embryo transfers (3.9% of all transfers) were complicated by finding retained embryos after the initial embryo transfer-all retained embryos were immediately retransferred. There was no difference in the frequency of retained embryos during oocyte retrieval versus thawed embryo cycles. The pregnancy, implantation, and delivery rates per embryo transfer were not negatively affected by embryo(s) retained in the transfer catheter. Age, fresh versus frozen embryo, use of ultrasound during the procedure, or transferring physician did not influence pregnancy outcome. CONCLUSION(S): Immediate retransfer of embryos retained in the catheter following the initial transfer attempt did not have an adverse effect on pregnancy outcome.     

An 18-month survey of infertility treatment by in vitro fertilization,gamete and zygote intrafallopian transfer,and replacement of frozen-thawed embryos

An 18-month survey of infertility treatment by in vitro fertilization (IVF) and related procedures at the Centre for Reproductive Medicine of the Vrije Universiteit Brussel is described. During this period, 1326 treatment cycles were started in patients with long-standing infertility and 1135 oocyte retrievals were performed in 771 different patients. IVF and embryo transfer (ET) after laparoscopic (N=793) or ultrasonically guided (N=342) ovum pickup, gamete intrafallopian transfer (GIFT;N=284), or zygote intrafallopian transfer (ZIFT;N=15) combined with IVF as well as the replacement of cryopreserved embryos yielded an overall pregnancy rate of 21.8% per started cycle. Echographic and laparoscopic oocyte retrieval gave similar results except for a higher fertilization rate after echographic-guided retrieval. For in vitro fertilization and embryo transfer an overall pregnancy rate of 26% per transfer was obtained. For GIFT and ZIFT the pregnancy rates were, respectively, 27.8 and 46.7% per replacement. For each procedure onethird of the pregnancies aborted. After the replacement of frozen and thawed embryos, during a natural cycle, a significantly lower fetal loss was observed.     

Congélation lente et vitrification des ovocytes humains matures et immatures

Performance and security questions in human oocyte cryopreservation have been taking researchers for about two decades. Oocytes are usually frozen at metaphase II. Immature oocytes cryopreservation is still a research alternative. Two techniques are currently available for oocyte cryopreservation: slow freezing and vitrification. Experimental data suggest that vitrification has less impact on oocyte physiology than classical slow freezing. After slow freezing of mature oocytes, survival and fertilization rates reach 70 to 80% whereas cleavage rates are around 90%, leading to five implantations and 1.2 births per 100 thawed oocytes. After vitrification of mature oocytes, survival and cleavage rates reach 90% leading to 11 implantations and 1.8 births per 100 thawed oocytes. The obstetrical and neonatal prognosis of these pregnancies is reassuring. No increased risk of congenital anomalies has been observed. However, further evaluation is needed to guarantee the safety of cryopreservation procedures. Immature oocyte cryopreservation is not currently perfected but some indications appear of great interest.     

A program for matched, anonymous oocyte donation

The authors' program for matched, anonymous oocyte donation has resulted in two successful pregnancies among the first eight oocyte recipients. All oocyte recipients to date have had ovarian failure or absence with premature ovarian failure the most common cause. All recipients were cycled on a program of incremental oral micronized estradiol and intramuscular progesterone-in-oil. Thirteen candidates for oocyte donation were screened to obtain 8 donors. One donor candidate was excluded because of her medical history. The psychological screening of 2 of the other donor candidates (who subsequently did not complete the donation cycle) revealed a primary motive of financial gain. In general, the psychological profiles of donor candidates revealed a high incidence of troubled families and either reproductive loss or loss of a parent. Ovarian stimulation of the donors followed our standard in vitro fertilization protocol. The recipients' exogenous steroid replacement continued until days 97 and 101, respectively, of the two gestations. Both pregnancies resulted in the delivery of normal singleton males--the first at 40 weeks, the second at 35 weeks.     

Non-homogeneous hyperechogenic echo pattern three days after frozen embryo transfer is associated with lower pregnancy rates

OBJECTIVE: To evaluate the association of mid-luteal phase echo patterns and pregnancy rates (PRs) following frozen embryo transfer (ET). METHODS: Sonographic evaluation of endometrial echo patterns was performed three days after ET in the first frozen ET cycle of women < 40 years of age who used their own oocytes as well as all donor oocyte recipients. RESULTS: The distribution of echo patterns and clinical PRs were similar in women using their own eggs and women who used donor oocytes; therefore all data was combined. The clinical PR was 49.5% with a hyperechogenic echo pattern vs 38.8% with a non-hyperechogenic pattern, p = .007. CONCLUSION: A larger study of frozen ET and mid-luteal echo pattern now demonstrates conclusions similar to the data from fresh ET in hyperstimulated in vitro fertilization (IVF)-ET cycles in that failure to attain a hyperechogenic echo pattern three days after ET is associated with lower pregnancy rates.     

同期体外受精-胚胎移植(IVF-ET)赠卵的临床应用

目的:探讨当前形势下中国赠卵的可行性、赠卵数、影响因素及存在的问题。方法:行IVF-ET并自愿捐卵的21例患者及同期接受赠卵并完成IVF-ET周期的23例患者,分析供、受双方的受精率、妊娠率和种植率。结果:23例患者共接受赠卵135枚,平均每周期接受卵子5.6±1.5枚,29个移植周期,12例妊娠,周期妊娠率为41.4%。供卵的21例患者,9个新鲜胚胎移植周期,2例妊娠;32个解冻胚胎移植周期,12例妊娠,冷冻移植周期的妊娠率为37.5%。供、受双方受精率、冷冻胚胎移植周期的妊娠率、累积妊娠率均无统计学差异(P>0.05)。结论:供卵者提供6个左右的卵子既不影响供卵者的妊娠,也能为受卵者提供一个良好的妊娠机会。     

The impact of early testicular sperm extraction or cryopreservation on the outcome of intracytoplasmic sperm injection--a randomized controlled study

Purpose : To compare the outcome of sperm extraction 24 h before ovum pickup and on the day of oocyte retrieval. Methods : A controlled study was performed to compare the outcome of 90 sperm extractions and in vitro sperm injection cycles performed in 54 patients. Results : Available fresh sperm for the sperm injection procedure and cryopreservation obtained on the day of ovum pickup were similar to sperm collected 1 day before (33.3% vs. 39.4%, respectively). Fertilization rate obtained with fresh sperm was also similar (48.9% vs. 54%), respectively. Clinical pregnancy rate was 38% vs. 22% per embryo transfer, respectively (P = 0.235). When comparing an additional 24 cycles with cryopreservation of sperm retrieved on the day of ovum pickup, as well as a day previously, no significance was noted in the parameters. Conclusions : Sperm retrieved 24 h before oocyte retrieval and used as fresh or frozen–thawed for sperm injection are as effective as those used on the day of ovum pickup.     

Follicle recruitment determines IVF productivity rate via the number of embryos frozen and subsequent transfers

IVF productivity rate is an index defined as the sum of all live births from either fresh or frozen embryo transfers arising from a single oocyte collection. This retrospective analysis over 9 continuous years used this index to understand the potential impact on pregnancy rates of milder stimulation regimens with associated reduced egg numbers. The productivity rate per collection increased in a linear and significant rate as more oocytes were recovered, more embryos frozen and more frozen embryo transfers contributed to pregnancy. This observation was true for women aged <35 years and less so for women aged 35–39 years but not for women aged 40 years and older. The contribution of frozen embryo transfer to the productivity rate rose in a linear manner, reaching over 40% of all live births with nine oocytes. The number of live births per oocyte, pronuclear embryos and thawed embryos decreased significantly but the number of live births per embryo transferred (fresh or frozen) rose with rising oocyte numbers, reflecting increasing opportunity for embryo selection. This study suggests that optimal benefits with minimal risks are gained from a model that includes both fresh and frozen transfers under stimulation generating between 8 and 12 eggs.Most of the costs and risks associated with an IVF cycle occur during the stimulation, egg collection and subsequent transfer of fresh embryos and ignore or treat separately the outcome from any subsequent frozen embryo transfers. We have used the term ‘productivity rate’ (or cumulative pregnancy rate per collection cycle) that includes outcomes from both fresh and frozen transfers as a tool to explore the impact of oocyte numbers on the ultimate chance of pregnancy. While the pregnancy rate for individual fresh and frozen transfers were largely unrelated to oocyte numbers, the cumulative chance of pregnancy rose significantly with the number of oocytes recovered. This was due to the increasing contribution of frozen embryo transfers to the overall chance of pregnancy producing more than half of all pregnancies above five oocytes. While the fertilization rate and embryo quality was independent of egg numbers, increasingly more embryos needed to be used to generate sufficient good-quality embryos for transfers as the egg numbers rose. The study found that 8–12 oocytes provided the highest cumulative chance of pregnancy with the least risk of either failed fertilization or ovarian hyperstimulation syndrome and this range could be used as a target number for individualized stimulation regimens.     

Cumulative pregnancy rates after transfer of fresh and thawed embryos

Frozen-thawed embryo transfer is an effective procedure that allows further possibilities of pregnancy in addition to those obtained after the fresh in vitro fertilization (IVF). In our follow-up study we analysed all fresh embryo transfer procedures and every frozen-thawed embryo transfer performed from January 2000 to December 2001 evaluating the cumulative pregnancy rates. The study population was divided into two groups according to the female age: <38 years (group I) and >38 years (group II). All the best embryos were chosen for transfer and all the supernumerary good quality embryos were cryopreserved on the day of transfer. The embryos were then thawed and manipulated using a new technique. In group I, 527 patients (619 cycles) underwent fresh embryo transfer and in 232 of them (238 cycles) the embryos were frozen (44% per patients and 38.4% per cycle). In group II, 156 patients (193 cycles) underwent fresh embryo transfer and in 14 of them (15 cycles) the embryos were frozen (9% per patient and 7.8% per cycle). The pregnancy rate of group I patients that had their supernumerary embryos frozen (232 patients and 238 cycles) was 47.4% per cycle and 48.7% per patient whereas in the same population of group II patients (14 patients and 15 cycles) the clinical pregnancy rate was 35.7% per cycle and 38.5% per patients. The cumulative clinical pregnancy rate after transfer of fresh and thawed embryos was: group I, 74% per cycle and 76% per patients; group II, 42.8% per cycle and 46.1% per patient. Frozen-thawed embryo transfer is a cost-effective practice.     

Cumulative pregnancy rates resulting from the use of fresh and frozen oocytes: 7 years' experience

Storing supernumerary embryos and transferring them later fully utilizes the reproductive potential of retrieved oocytes, allowing a significant increase in the overall number of pregnancies achieved from a single cycle of ovarian stimulation treatment. As an alternative to embryo cryopreservation, preservation of unfertilized oocytes has been proposed to maximize clinical outcome. This paper presents data concerning the cumulative pregnancy rate after use of fresh and cryopreserved oocytes. In 80 treatment cycles in which patients chose to have only a few fresh oocytes inseminated, 24 pregnancies were obtained (30.0%), with an implantation rate of 22.6%. After cryopreservation with the standard slow-cooling protocol, the survival, fertilization and cleavage rates of 918 frozen oocytes were 43.4, 51.5 and 86.0% respectively. A total of 14 frozen pregnancies were achieved, with pregnancy rate 19.2% per transfer and implantation rate 12.3%. The cumulative pregnancy rate was 47.5% per patient. Therefore, despite a low rate of oocyte post-thaw survival, it appears that oocyte storage appreciably improves the number of pregnancies per treatment cycle in cases in which only a minority of oocytes are destined for the fresh treatment. This outcome provides valuable information for appraising the chances of clinical success when the option of embryo cryopreservation is not available.