hcg, or gnrh agonists, and often accompanied by estradiol, to increase the success rate of implantation and early embryogenesis, thereby complementing and/or supporting the function of the corpus luteum. a cochrane review found that hcg or progesterone given during the luteal phase may be associated with higher rates of live birth or ongoing pregnancy, but that the evidence is not conclusive. co-treatment with gnrh agonists appears to improve outcomes, by a live birth rate rd of +16% (95% confidence interval +10 to +22%). on the other hand, growth hormone or aspirin as adjunctive medication in ivf have no evidence of overall benefit. expansions there are various expansions or additional techniques that can be applied in ivf, which are usually not necessary for the ivf procedure itself, but would be virtually impossible or technically difficult to perform without concomitantly performing methods of ivf. preimplantation genetic screening or diagnosis main article: preimplantation genetic diagnosis preimplantation genetic screening (pgs) or preimplantation genetic diagnosis (pgd) has been suggested to be able to be used in ivf to select an embryo that appears to have the greatest chances for successful pregnancy. however, a systematic review and meta-analysis of existing randomised controlled trials came to the result that there is no evidence of a beneficial effect of pgs with cleavage-stage biopsy as measured by live birth rate. on the contrary, for women of advanced maternal age, pgs with cleavage-stage biopsy significantly lowers the live birth rate. technical drawbacks, such as the invasiveness of the biopsy, and non-representative samples because of mosaicism are the major underlying factors for inefficacy of pgs. still, as an expansion of ivf, patients who can benefit from pgs/pgd include: couples who have a family history of inherited disease couples who want prenatal sex discernment. this can be used to diagnose monogenic disorders with sex linkage. it can potentially be used for sex selection, wherein a fetus is aborted if having an undesired sex. couples who already have a child with an incurable disease and need compatible cells from a second healthy child to cure the first, resulting in a "saviour sibling" that matches the sick child in hla type. pgs screens for numeral chromosomal abnormalities while pgd diagnosis the specific molecular defect of the inherited disease. in both pgs and pgd, individual cells from a pre-embryo, or preferably trophectoderm cells biopsied from a blastocyst, are analysed during the ivf process. before the transfer of a pre-embryo back to a woman's uterus, one or two cells are removed from the pre-embryos (8-cell stage), or preferably from a blastocyst. these cells are then evaluated for normality. typically within one to two days, following completion of the evaluation, only the normal pre-embryos are transferred back to the woman's uterus. alternatively, a blastocyst can be cryopreserved via vitrification and transferred at a later date to the uterus. in addition, pgs can significantly reduce the risk of multiple pregnancies because fewer embryos, ideally just one, are needed for implantation. cryopreservation main articles: oocyte cryopreservation and embryo cryopreservation cryopreservation can be performed as oocyte cryopreservation before fertilisation, or as embryo cryopreservation after fertilisation. the rand consulting group has estimated there to be 400,000 frozen embryos in the united states in 2006. the advantage is that patients who fail to conceive may become pregnant using such embryos without having to go through a full ivf cycle. or, if pregnancy occurred, they could return later for another pregnancy. spare oocytes or embryos resulting from fertility treatments may be used for oocyte donation or embryo donation to another woman or couple, and embryos may be created, frozen and stored specifically for transfer and donation by using donor eggs and sperm. also, oocyte cryopreservation can be used for women who are likely to lose their ovarian reserve due to undergoing chemotherapy. by 2017, many centers have adopted embryo cryopreservation as their primary ivf therapy, and perform few or no fresh embryo transfers. the two main reasons for this have been better endometrial receptivity when embryos are transferred in cycles without exposure to ovarian stimulation and also the ability to store the embryos while awaiting the results of preimplantation genetic testing. the outcome from using cryopreserved embryos has uniformly been positive with no increase in birth defects or development abnormalities. other expansions intracytoplasmic sperm injection (icsi) is where a single sperm is injected directly into an egg. its main usage as an expansion of ivf is to overcome male infertility problems, although it may also be used where eggs cannot easily be penetrated by sperm, and occasionally in conjunction with sperm donation. it can be used in teratozoospermia, since once the egg is fertilised abnormal sperm morphology does not appear to influence blastocyst development or blastocyst morphology. additional methods of embryo profiling. for example, methods are emerging in making comprehensive analyses of up to entire genomes, transcriptomes, proteomes and metabolomes which may be used to score embryos by comparing the patterns with ones that have previously been found among embryos in successful versus unsuccessful pregnancies. assisted zona hatching (azh) can be performed shortly before the embryo is transferred to the uterus. a small opening is made in the outer layer surrounding the egg in order to help the embryo hatch out and aid in the implantation process of the growing embryo. in egg donation and embryo donation, the resultant embryo after fertilisation is inserted in another woman than the one providing the eggs. these are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful ivf cycles or advanced maternal age. in the egg donor process, eggs are retrieved from a donor's ovaries, fertilised in the laboratory with the sperm from the recipient's partner, and the resulting healthy embryos are returned to the recipient's uterus. in oocyte selection, the oocytes with optimal chances of live birth can be chosen. it can also be used as a means of preimplantation genetic screening. embryo splitting can be used for twinning to increase the number of available embryos. cytoplasmic transfer is where the cytoplasm from a donor egg is injected into an egg with compromised mitochondria. the resulting egg is then fertilised with sperm and introduced into a womb, usually that of the woman who provided the recipient egg and nuclear dna. cytoplasmic transfer was created to aid women who experience infertility due to deficient or damaged mitochondria, contained within an egg's cytoplasm. leftover embryos or eggs further information: embryo donation and egg donor there may be leftover embryos or eggs from ivf procedures if the woman for whom they were originally created has successfully carried one or more pregnancies to term, and no longer wishes to use them. with the woman's or couple's permission, these may be donated to help other women or couples as a means of third party reproduction. in embryo donation, these extra embryos are given to other couples or women for transfer, with the goal of producing a successful pregnancy. embryo recipients typically have genetic issues or poor-quality embryos or eggs of their own. the resulting child is considered the child of the woman who carries it and gives birth, and not the child of the donor, the same as occurs with egg donation or sperm donation. typically, genetic parents donate the eggs or embryos to a fertility clinic where they are preserved by oocyte cryopreservation or embryo cryopreservation until a carrier is found for them. typically the process of matching the donation with the prospective parents is conducted by the agency itself, at which time the clinic transfers ownership of the embryos to the prospective parents. in the united states, women seeking to be an embryo recipient undergo infectious disease screening required by the food and drug administration (fda), and reproductive tests to determine the best placement location and cycle timing before the actual embryo transfer occurs. the amount of screening the embryo has already undergone is largely dependent on the genetic parents' own ivf clinic and process. the embryo recipient may elect to have her own embryologist conduct further testing. alternatives to donating unused embryos are destroying them (or having them transferred at a time when pregnancy is very unlikely), keeping them frozen indefinitely, or donating them for use in research (which results in their unviability). individual moral views on disposing of leftover embryos may depend on personal views on the beginning of human personhood and the definition and/or value of potential future persons, and on the value that is given to fundamental research questions. some people believe donation of leftover embryos for research is a good alternative to discarding the embryos when patients receive proper, honest and clear information about the research project, the procedures and the scientific values. complications multiple births the major complication of ivf is the risk of multiple births. this is directly related to the practice of transferring multiple embryos at embryo transfer. multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. britain, belgium) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. a double blind, randomised study followed ivf pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of less than 2,500 grams (5.5 lb). there is some evidence that making a double embryo transfer during one cycle achieves a higher live birth rate than a single embryo transfer; but making two single embryo transfers in two cycles has the same live birth rate and would avoid multiple pregnancies. sex ratio distortions certain kinds of ivf have been shown to lead to distortions in the sex ratio at birth. intracytoplasmic sperm injection (icsi), which was first applied in 1991, leads to slightly more female births (51.3% female). blastocyst transfer, which was first applied in 1984, leads to significantly more male births (56.1% male). standard ivf done at the second or third day leads to a normal sex ratio. epigenetic modifications caused by extended culture leading to the death of more female embryos has been theorized as the reason why blastocyst transfer leads to a higher male sex ratio; however, adding retinoic acid to the culture can bring this ratio back to normal. a second theory is that the male-biased sex ratio may due to a higher rate of selection of male embryos. male embryos develop faster in vitro, and thus may appear more viable for transfer. spread of infectious disease by sperm washing, the risk that a chronic disease in the individual providing the sperm would infect the female or offspring can be brought to negligible levels. in males with hepatitis b, the practice committee of the american society for reproductive medicine advises that sperm washing is not necessary in ivf to prevent transmission, unless the female partner has not been effectively vaccinated. in females with hepatitis b, the risk of vertical transmission during ivf is no different from the risk in spontaneous conception. however, there is not enough evidence to say that icsi procedures are safe in females with hepatitis b in regard to vertical transmission to the offspring. regarding potential spread of hiv/aids, japan's government prohibited the use of ivf procedures for couples in which both partners are infected with hiv. despite the fact that the ethics committees previously allowed the ogikubo, tokyo hospital, located in tokyo, to use ivf for couples with hiv, the ministry of health, labour and welfare of japan decided to block the practice. hideji hanabusa, the vice president of the ogikubo hospital, states that together with his colleagues, he managed to develop a method through which scientists are able to remove hiv from sperm. other risks to the egg provider/retriever a risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome, particularly if hcg is used for inducing final oocyte maturation. this results in swollen, painful ovaries. it occurs in 30% of patients. mild cases can be treated with over the counter medications and cases