Author information:

  • 1Department of Reproductive Endocrinology and Infertility, New Hope Fertility Center , New York, NY , USA and.

Abstract

OBJECTIVE:

The objective of this study was to assess the relationship between BMI and oocyte number and maturity in participants who underwent minimal stimulation (mini-) or conventional IVF.

METHODS:

Participants who underwent their first autologous cycle of either conventional (n = 219) or mini-IVF (n = 220) were divided according to their BMI to analyze IVF outcome parameters. The main outcome measure was the number of oocytes in metaphase II (MII). Secondary outcomes included the number of total oocytes retrieved, fertilized (2PN) oocytes, cleavage and blastocyst stage embryos, clinical pregnancy (CP), and live birth (LB) rates.

RESULTS:

In conventional IVF, but not in mini-IVF, the number of total oocytes retrieved (14.5 ± 0.8 versus 8.8 ± 1.3) and MII oocytes (11.2 ± 0.7 versus 7.1 ± 1.1) were significantly lower in obese compared with normal BMI women. Multivariable linear regression adjusting for age, day 3 FSH, days of stimulation, and total gonadotropin dose demonstrated that BMI was an independent predictor of the number of MII oocytes in conventional IVF (p = 0.0004). Additionally, only in conventional IVF, BMI was negatively correlated with the total number of 2PN oocytes, as well as the number of cleavage stage embryos.

CONCLUSIONS:

Female adiposity might impair oocyte number and maturity in conventional IVF but not in mini-IVF. These data suggest that mild ovarian stimulation might yield healthier oocytes in obese women.


GV transfer provides a unique model for future studies designed to identify the cytoplasmic factors that could restore resumption of meiosis in arrested oocytes or oocytes not responsive to gonadotropins. The abnormal assembly of meiotic spindle is believed to be a major mechanism for aneuploidy, a major cause for age-related infertility in women. GV transfer may provide a potential therapeutic option for women who suffer from age-related infertility by transferring the GV from an older womans oocyte into a donated cytoplasm from a young woman. It is only by considering all aspects of maturation, particularly the cytoplasm, that the production of in vitro mature human oocytes with live-birth producing potential will be achieved. GV transfer represents a unique technology that can overcome chromosomal abnormalities in oocytes from aged individuals and holds the promise for prevention of aneuploidy in women with diminished ovarian reserve.

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Developmental incompetency of denuded mouse oocytes undergoing maturation in vitro is ooplasmic in nature and is associated with aberrant Oct-4 expression. (abstract)

Metaphase II nuclei generated by germinal vesicle transfer in mouse oocytes support embryonic development to term. (abstract)

Ooplasmic influence on nuclear function during the metaphase II-interphase transition in mouse oocytes. (abstract)

Fertility and maternal age strategies to improve pregnancy outcome. (abstract)

In-vitro development of mouse zygotes following reconstruction by sequential transfer of germinal vesicles and haploid pronuclei. (abstract)

Reconstruction of mouse oocytes by germinal vesicle transfer: maturity of host oocyte cytoplasm determines meiosis. (abstract)

In vitro maturation of human preovulatory oocytes reconstructed by germinal vesicle transfer. (abstract)

In vitro development of human triploid zygotes reconstructed by pronuclear transfer. (abstract)

Germinal vesicle xeno-transfer between mouse and human oocytes: A model to study ooplasmic influences on meiotic division. (abstract)

Pregnancy derived from human nuclear transfer. (abstract)


Time-lapse monitoring combined with array CGH improves implantation and ongoing pregnancy rates according to study

Recent advances in time-lapse monitoring in IVF treatment have presented new morphokinetic markers for identifying and selecting embryos with high implantation probabilities. Are implantation outcomes improved when time lapse monitoring is combined with conventional array CGH testing in patients undergoing preimplantation genetic screening?

A study involving 138 PGS patients with a mean age of 36.6 plus/minus 2.4 years, concludes that using both technologies together to select competent blastocysts for transfer, improves the rates for both implantation and ongoing pregnancy.

1163 sibling MII oocytes were randomized into two groups. In Group A, oocytes were cultured using time-lapse technology. Group B oocytes were cultured in a conventional incubator. Both oocyte groups underwent whole genomic amplification and array CGH after trophectoderm biopsy on day 5. One to two euploid blastocysts were selected from each group for transfer to individual patients on day 6. Ongoing pregnancy and implantation rates were then compared.

The study showed significant differences in clinical pregnancy rates between the two groups, 71.1% for the group using time lapse techniques vs. 45.9% for the group cultured conventionally. Observed implantation rates per embryo transfer increased significantly as well in Group A as compared to Group B. Ongoing pregnancy rates also increased significantly in Group A (68.9%) vs. Group B (40.5%). There was no significant difference in miscarriage rates between the two groups.

This is the first study of its kind using sibling oocytes to evaluate the efficiency of methods for selecting competent blastocysts for transfer. For PGS patients, the data clearly shows the benefits of using both time lapse and array CGH.



Aneuploidy screening of human blastocysts from PGS patients using next generation sequencing: a pilot study

Study shows Next Generation Sequencing (NGS) detects all types of chromosomal abnormalities in human blastocysts; may improve pregnancy and implantation rates for PGS patients

Advances in next-generation sequencing offer new ways of detecting DNA mutations and chromosomal aberrations—otherwise known as aneuploidy—for general diagnostic purposes. Are these new sequencing methods a useful tool for IVF patients undergoing preimplantation genetic screening?

A blind study of 56 blastocysts from 15 PGS patients concludes that NGS was able to detect all type of aneuploidies, including monosomy, trisomy, and dual and complex chromosomal abnormalities, as accurately and efficiently traditional array CGH testing.

Blastocysts from PGS patients with a mean age of 38.3 plus/minus 1.7 years were biopsied and vitrified on day 5 of the cycle. Whole genomic amplification of embryonic DNA was performed and analyzed blindly using both NGS and array CGH techniques. The NGS technique proved 100% equivalent to array CGH technique for detecting all forms of aneuploidies. It should be noted that the study was limited to embryos from PGS patients with recurrent pregnancy loss and previous aneuploidy conceptions. Further randomized clinical trials are planned to determine whether these results will extrapolate to all IV patients.

The study also showed that NGS screening is extremely useful for identifying euploid blastocysts for transfer. Such blastocysts were identified in seven out of eight PGS patients, and were then thawed and implanted. 71.4% of the patients became pregnant with gestation sacs and fetal heart beats. The implantation rate per embryo transfer reached 72.2%.

For women with unknown recurrent pregnancy loss and previous aneuploidy conceptions, NGS sequencing is an accurate means of identifying aneuploidies in blastocysts and may also offer additional advantages over array CGH.



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Pregnancy and live birth following the transfer of vitrified–warmed blastocysts derived from zona- and corona-cell-free oocytes reproduction

A 28-year-old patient presented for preimplantation genetic screening (PGS) for family balancing utilizing previously vitrified blastocysts and day-2 embryos. To synchronize endometrial development with the embryos to be transferred, five embryos vitrified on day 2 were warmed 3days prior to scheduled transfer. Three of them developed to 8-, 8- and 7-cell stages, respectively, and were biopsied the next day, during which three vitrified blastocysts were warmed and the two surviving blastocysts underwent trophectoderm biopsy. The five biopsied embryos were subjected to two-probe fluorescence in-situ hybridization for chromosomes X and Y. As there were still 2days before the scheduled embryo transfer following biopsy, the two biopsied blastocysts were re-vitrified. One blastocyst and two of the embryos vitrified on day 2 were normal for sex chromosomes; of these, one of the day-2 vitrified embryos was arrested and the other did not favour the patient’s wish. The re-vitrified blastocyst, which was normal for sex chromosomes, was therefore warmed and transferred, resulting in delivery of one healthy boy. As far as is known, this is the first-reported live birth developed from a re-vitrified blastocyst that had been previously vitrified, warmed and undergone trophectoderm biopsy.


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Minimal ovarian stimulation (Mini-IVF™) for IVF utilizing vitrification and cryopreserved embryo transfer

Gentle ovarian stimulation protocols, such as ‘mini-IVF’, have several potential advantages over conventional IVF protocols, including less medication and fewer injections, producing fewer eggs, but eggs of higher quality. The particular ‘mild’ stimulation protocol called ‘mini-IVF’ is described. This protocol requires a reliable and cheap method for embryo cryopreservation such as vitrification, because of the negative impact of clomiphene citrate on the endometrium and since cryopreserved embryo transfers with this protocol have yielded much higher pregnancy rates than fresh transfers. In this series, patients were not denied treatment based on their day-3 FSH value or ovarian reserve. Yet very acceptable pregnancy rates were achieved (20% for fresh embryo transfers and 41% for cryopreserved embryo transfers). These results strengthen the argument for a mini-IVF protocol and vitrification as an alternative to standard conventional IVF stimulation protocols. Now a randomized control trial with cryopreserved single-embryo transfer is required.

Gentle ovarian stimulation protocols have several potential advantages over conventional IVF protocols, including less medication and fewer injections, producing fewer eggs, but eggs of higher quality. ‘Mini-IVF’ is safe, patient friendly and physiologically more natural. It may be more cost effective if results are comparable to conventional protocols. Vitrification of embryos allows the transfer of warmed embryos in subsequent cycles when the endometrium is more receptive. In this series, patients were not denied treatment based on their day-3 FSH value or ovarian reserve. Yet very acceptable pregnancy rates were achieved (20% for fresh embryo transfers and 41% for cryopreserved embryo transfers). These results strengthen the argument for gentle stimulation protocols and vitrification in preference to standard conventional IVF stimulation protocols. Now a randomized control trial with cryopreserved single-embryo transfer is required.


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Comparison of blastocyst formation between standard and clomiphene citrate (CC) stimulated in vitro fertilization (IVF) cycles” – ASRM, Oct. 2005

Poster Presentation for the American Society For Reproductive Medicine (ASRM), October 17-19, 2005, Montreal, Quebec

[P-447] Comparison of blastocyst formation between standard and clomiphene citrate (CC) stimulated in vitro fertilization (IVF) cycles.

J. Zhang, Q. Zhan, T. Okimura, K. Kato, S. Silber, O. Kato. New Hope Fertility Center, New York, NY; Center for IVF, 1st Affiliated Hospital of Zhong Shan University, Guangzhou, China; Kato Ladies Clinic, Tokyo, Japan; St Louis Fertility Center, St Louis, MO

Dr. Zhang submitted the following paper to the American Society of Reproductive Medicine (ASRM) conference in October 2005 in Montreal, Quebec. For those interested in the pure science elements of minimum stimulation, this explains the basis for our advanced procedure in some detail.



Dr. Sherman Silber says he can extend a woman’s fertility by decades. He just needs to freeze her eggs or even a piece of her ovarian tissue.

By Chad Garrison, The Riverfront Times, Oct. 4, 2007

Ovarian Tissue Transfer involves removing the ovary of one woman, microsurgically dissecting the tissue and subsequently transplanting it into another woman. This procedure is often considered a donor procedure, whereby an infertile woman receives the ovarian tissue of a fertile woman. In this case, it is a preferable alternative to egg donation because ovarian tissue has potentially thousands of eggs and the tissue continues to function as a normal healthy ovary in the recipient’s body long after transfer, so it offers recipients multiple chances at pregnancy as compared with the single chance offered by egg donation.

Ovarian Tissue Transfer also occurs when a woman has elected to freeze her own ovarian reserve and then have it transferred back when she is ready to have a child. That is, instead of freezing individual eggs, the patient has the entire ovarian reserve frozen. This procedure is preferable to egg freezing because one egg-freezing cycle generally preserves 1-5 quality eggs, whereas Ovarian Tissue Transfer freezes tens, to hundreds, to thousands of eggs, depending on the woman.